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Published in: Immunity & Ageing 1/2011

Open Access 01-12-2011 | Research

Aging impacts isolated lymphoid follicle development and function

Authors: Keely G McDonald, Matthew R Leach, Conway Huang, Caihong Wang, Rodney D Newberry

Published in: Immunity & Ageing | Issue 1/2011

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Abstract

Background

Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures that arise from nascent lymphoid tissues, or cryptopatches (CP), in response to local inflammatory stimuli. ILFs promote "homeostatic" responses including the production of antigen-specific IgA, thus playing a key role in mucosal immune protection. ILF dysfunction with aging could contribute to immunosenescence of the mucosal system, and accordingly we examined phenotypic and functional aspects of ILFs from young (2 month old) and aged (2 year old) mice.

Results

We observed that aged mice have increased numbers of ILFs and increased numbers of structures corresponding to an early stage of CPs transforming into ILFs. The cellular composition of ILFs in aged mice is altered with a smaller B-lymphocyte population and an increased T-lymphocyte population. The ILF T-lymphocyte population is notable by the presence of CD4+ CD8αα+ T-lymphocytes, which are absent from the systemic compartment. The smaller B-lymphocyte population in ILFs from aged mice is directly correlated with decreased mRNA and protein expression of CCL20 and CXCL13, two chemokines that play crucial roles in recruiting B-lymphocytes into ILFs. Aged mice had elevated levels of serum and fecal immunoglobulins and despite the decreased B-lymphocyte population, ILFs from aged mice displayed increased IgA production. The immunoglobulin repertoire was skewed in aged mice, and ILFs demonstrated a repertoire usage similar to that of the systemic pool in both young and aged mice.

Conclusions

Here we observed that ILF development, cellular composition, and immunoglobulin production are altered with aging suggesting that ILF dysfunction contributes to mucosal immunosenescence.
Appendix
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Literature
1.
go back to reference Castle SC, Uyemura K, Rafi A, Akande O, Makinodan T: Comorbidity is a better predictor of impaired immunity than chronological age in older adults. J Am Geriatr Soc. 2005, 53 (9): 1565-1569. 10.1111/j.1532-5415.2005.53512.x.PubMed Castle SC, Uyemura K, Rafi A, Akande O, Makinodan T: Comorbidity is a better predictor of impaired immunity than chronological age in older adults. J Am Geriatr Soc. 2005, 53 (9): 1565-1569. 10.1111/j.1532-5415.2005.53512.x.PubMed
2.
go back to reference Castle SC, Uyemura K, Fulop T, Makinodan T: Host resistance and immune responses in advanced age. Clin Geriatr Med. 2007, 23 (3): 463-479. 10.1016/j.cger.2007.03.005.PubMed Castle SC, Uyemura K, Fulop T, Makinodan T: Host resistance and immune responses in advanced age. Clin Geriatr Med. 2007, 23 (3): 463-479. 10.1016/j.cger.2007.03.005.PubMed
3.
go back to reference Castle SC: Impact of age-related immune dysfunction on risk of infections. Z Gerontol Geriatr. 2000, 33 (5): 341-349. 10.1007/s003910070030.PubMed Castle SC: Impact of age-related immune dysfunction on risk of infections. Z Gerontol Geriatr. 2000, 33 (5): 341-349. 10.1007/s003910070030.PubMed
4.
go back to reference Pawelec G: Immunosenescence: impact in the young as well as the old?. Mech Ageing Dev. 1999, 108 (1): 1-7. 10.1016/S0047-6374(99)00010-X.PubMed Pawelec G: Immunosenescence: impact in the young as well as the old?. Mech Ageing Dev. 1999, 108 (1): 1-7. 10.1016/S0047-6374(99)00010-X.PubMed
5.
go back to reference Hakim FT, Gress RE: Immunosenescence: deficits in adaptive immunity in the elderly. Tissue Antigens. 2007, 70 (3): 179-189. 10.1111/j.1399-0039.2007.00891.x.PubMed Hakim FT, Gress RE: Immunosenescence: deficits in adaptive immunity in the elderly. Tissue Antigens. 2007, 70 (3): 179-189. 10.1111/j.1399-0039.2007.00891.x.PubMed
6.
go back to reference Janssens JP, Krause KH: Pneumonia in the very old. Lancet Infect Dis. 2004, 4 (2): 112-124. 10.1016/S1473-3099(04)00931-4.PubMed Janssens JP, Krause KH: Pneumonia in the very old. Lancet Infect Dis. 2004, 4 (2): 112-124. 10.1016/S1473-3099(04)00931-4.PubMed
7.
go back to reference Castle SC: Clinical relevance of age-related immune dysfunction. Clin Infect Dis. 2000, 31 (2): 578-585. 10.1086/313947.PubMed Castle SC: Clinical relevance of age-related immune dysfunction. Clin Infect Dis. 2000, 31 (2): 578-585. 10.1086/313947.PubMed
8.
go back to reference Bouree P: Immunity and immunization in elderly. Pathol Biol (Paris). 2003, 51 (10): 581-585. Bouree P: Immunity and immunization in elderly. Pathol Biol (Paris). 2003, 51 (10): 581-585.
9.
go back to reference Kang I, Hong MS, Nolasco H, Park SH, Dan JM, Choi JY, Craft J: Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine. J Immunol. 2004, 173 (1): 673-681.PubMed Kang I, Hong MS, Nolasco H, Park SH, Dan JM, Choi JY, Craft J: Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine. J Immunol. 2004, 173 (1): 673-681.PubMed
10.
go back to reference Zhang HG, Grizzle WE: Aging, immunity, and tumor susceptibility. Immunol Allergy Clin North Am. 2003, 23 (1): 83-102. 10.1016/S0889-8561(02)00085-1.PubMed Zhang HG, Grizzle WE: Aging, immunity, and tumor susceptibility. Immunol Allergy Clin North Am. 2003, 23 (1): 83-102. 10.1016/S0889-8561(02)00085-1.PubMed
11.
go back to reference Johnson SA, Cambier JC: Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity. Arthritis Res Ther. 2004, 6 (4): 131-139. 10.1186/ar1180.PubMedCentralPubMed Johnson SA, Cambier JC: Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity. Arthritis Res Ther. 2004, 6 (4): 131-139. 10.1186/ar1180.PubMedCentralPubMed
12.
go back to reference Schmucker DL, Heyworth MF, Owen RL, Daniels CK: Impact of aging on gastrointestinal mucosal immunity. Dig Dis Sci. 1996, 41 (6): 1183-1193. 10.1007/BF02088236.PubMed Schmucker DL, Heyworth MF, Owen RL, Daniels CK: Impact of aging on gastrointestinal mucosal immunity. Dig Dis Sci. 1996, 41 (6): 1183-1193. 10.1007/BF02088236.PubMed
13.
go back to reference Schmucker DL, Owen RL, Outenreath R, Thoreux K: Basis for the age-related decline in intestinal mucosal immunity. Clin Dev Immunol. 2003, 10 (2-4): 167-172. 10.1080/10446670310001642168.PubMedCentralPubMed Schmucker DL, Owen RL, Outenreath R, Thoreux K: Basis for the age-related decline in intestinal mucosal immunity. Clin Dev Immunol. 2003, 10 (2-4): 167-172. 10.1080/10446670310001642168.PubMedCentralPubMed
14.
go back to reference Fujihashi K, McGhee JR: Mucosal immunity and tolerance in the elderly. Mech Ageing Dev. 2004, 125 (12): 889-898. 10.1016/j.mad.2004.05.009.PubMed Fujihashi K, McGhee JR: Mucosal immunity and tolerance in the elderly. Mech Ageing Dev. 2004, 125 (12): 889-898. 10.1016/j.mad.2004.05.009.PubMed
15.
go back to reference Lindner AE: Inflammatory bowel disease in the elderly. Clin Geriatr Med. 1999, 15 (3): 487-497.PubMed Lindner AE: Inflammatory bowel disease in the elderly. Clin Geriatr Med. 1999, 15 (3): 487-497.PubMed
16.
go back to reference Grimm IS, Friedman LS: Inflammatory bowel disease in the elderly. Gastroenterol Clin North Am. 1990, 19 (2): 361-389.PubMed Grimm IS, Friedman LS: Inflammatory bowel disease in the elderly. Gastroenterol Clin North Am. 1990, 19 (2): 361-389.PubMed
17.
go back to reference McDonald KG, McDonough JS, Newberry RD: Adaptive immune responses are dispensable for isolated lymphoid follicle formation: antigen-naive, lymphotoxin-sufficient B lymphocytes drive the formation of mature isolated lymphoid follicles. J Immunol. 2005, 174 (9): 5720-5728.PubMed McDonald KG, McDonough JS, Newberry RD: Adaptive immune responses are dispensable for isolated lymphoid follicle formation: antigen-naive, lymphotoxin-sufficient B lymphocytes drive the formation of mature isolated lymphoid follicles. J Immunol. 2005, 174 (9): 5720-5728.PubMed
18.
go back to reference McDonald KG, McDonough JS, Wang C, Kucharzik T, Williams IR, Newberry RD: CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles. Am J Pathol. 2007, 170 (4): 1229-1240. 10.2353/ajpath.2007.060817.PubMedCentralPubMed McDonald KG, McDonough JS, Wang C, Kucharzik T, Williams IR, Newberry RD: CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles. Am J Pathol. 2007, 170 (4): 1229-1240. 10.2353/ajpath.2007.060817.PubMedCentralPubMed
19.
go back to reference Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, Kaminogawa S, Takahashi-Iwanaga H, Iwanaga T, Kiyono H: Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol. 2002, 168 (1): 57-64.PubMed Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, Kaminogawa S, Takahashi-Iwanaga H, Iwanaga T, Kiyono H: Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol. 2002, 168 (1): 57-64.PubMed
20.
go back to reference Lorenz RG, Chaplin DD, McDonald KG, McDonough JS, Newberry RD: Isolated Lymphoid Follicle Formation Is Inducible and Dependent Upon Lymphotoxin-Sufficient B Lymphocytes, Lymphotoxin beta Receptor, and TNF Receptor I Function. J Immunol. 2003, 170 (11): 5475-5482.PubMed Lorenz RG, Chaplin DD, McDonald KG, McDonough JS, Newberry RD: Isolated Lymphoid Follicle Formation Is Inducible and Dependent Upon Lymphotoxin-Sufficient B Lymphocytes, Lymphotoxin beta Receptor, and TNF Receptor I Function. J Immunol. 2003, 170 (11): 5475-5482.PubMed
21.
go back to reference Lorenz RG, Newberry RD: Isolated Lymphoid Follicles Can Function as Sites for Induction of Mucosal Immune Responses. Ann N Y Acad Sci. 2004, 1029: 44-57. 10.1196/annals.1309.006.PubMed Lorenz RG, Newberry RD: Isolated Lymphoid Follicles Can Function as Sites for Induction of Mucosal Immune Responses. Ann N Y Acad Sci. 2004, 1029: 44-57. 10.1196/annals.1309.006.PubMed
22.
go back to reference Wang C, McDonald KG, McDonough JS, Newberry RD: Murine isolated lymphoid follicles contain follicular B-lymphocytes with a mucosal phenotype. Am J Physiol Gastrointest Liver Physiol. 2006, 291 (4): G595-604. 10.1152/ajpgi.00525.2005. Epub 2006 Jun 15PubMedCentralPubMed Wang C, McDonald KG, McDonough JS, Newberry RD: Murine isolated lymphoid follicles contain follicular B-lymphocytes with a mucosal phenotype. Am J Physiol Gastrointest Liver Physiol. 2006, 291 (4): G595-604. 10.1152/ajpgi.00525.2005. Epub 2006 Jun 15PubMedCentralPubMed
23.
go back to reference McDonald KG, McDonough JS, Dieckgraefe BK, Newberry RD: Dendritic cells produce CXCL13 and participate in the development of murine small intestine lymphoid tissues. Am J Pathol. 176 (5): 2367-2377. 10.2353/ajpath.2010.090723. McDonald KG, McDonough JS, Dieckgraefe BK, Newberry RD: Dendritic cells produce CXCL13 and participate in the development of murine small intestine lymphoid tissues. Am J Pathol. 176 (5): 2367-2377. 10.2353/ajpath.2010.090723.
24.
go back to reference Ansel KM, Ngo VN, Hyman PL, Luther SA, Forster R, Sedgwick JD, Browning JL, Lipp M, Cyster JG: A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature. 2000, 406 (6793): 309-314. 10.1038/35018581.PubMed Ansel KM, Ngo VN, Hyman PL, Luther SA, Forster R, Sedgwick JD, Browning JL, Lipp M, Cyster JG: A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature. 2000, 406 (6793): 309-314. 10.1038/35018581.PubMed
25.
go back to reference Velaga S, Herbrand H, Friedrichsen M, Jiong T, Dorsch M, Hoffmann MW, Forster R, Pabst O: Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses. J Immunol. 2009, 182 (5): 2610-2619. 10.4049/jimmunol.0801141.PubMed Velaga S, Herbrand H, Friedrichsen M, Jiong T, Dorsch M, Hoffmann MW, Forster R, Pabst O: Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses. J Immunol. 2009, 182 (5): 2610-2619. 10.4049/jimmunol.0801141.PubMed
26.
go back to reference Schmucker DL, Thoreux K, Owen RL: Aging impairs intestinal immunity. Mech Ageing Dev. 2001, 122 (13): 1397-1411. 10.1016/S0047-6374(01)00276-7.PubMed Schmucker DL, Thoreux K, Owen RL: Aging impairs intestinal immunity. Mech Ageing Dev. 2001, 122 (13): 1397-1411. 10.1016/S0047-6374(01)00276-7.PubMed
27.
go back to reference Finkelstein MS, Tanner M, Freedman ML: Salivary and serum IgA levels in a geriatric outpatient population. J Clin Immunol. 1984, 4 (2): 85-91. 10.1007/BF00915040.PubMed Finkelstein MS, Tanner M, Freedman ML: Salivary and serum IgA levels in a geriatric outpatient population. J Clin Immunol. 1984, 4 (2): 85-91. 10.1007/BF00915040.PubMed
28.
go back to reference Arranz E, O'Mahony S, Barton JR, Ferguson A: Immunosenescence and mucosal immunity: significant effects of old age on secretory IgA concentrations and intraepithelial lymphocyte counts. Gut. 1992, 33 (7): 882-886. 10.1136/gut.33.7.882.PubMedCentralPubMed Arranz E, O'Mahony S, Barton JR, Ferguson A: Immunosenescence and mucosal immunity: significant effects of old age on secretory IgA concentrations and intraepithelial lymphocyte counts. Gut. 1992, 33 (7): 882-886. 10.1136/gut.33.7.882.PubMedCentralPubMed
29.
go back to reference Koga T, McGhee JR, Kato H, Kato R, Kiyono H, Fujihashi K: Evidence for early aging in the mucosal immune system. J Immunol. 2000, 165 (9): 5352-5359.PubMed Koga T, McGhee JR, Kato H, Kato R, Kiyono H, Fujihashi K: Evidence for early aging in the mucosal immune system. J Immunol. 2000, 165 (9): 5352-5359.PubMed
30.
go back to reference Penn ND, Purkins L, Kelleher J, Heatley RV, Mascie-Taylor BH: Ageing and duodenal mucosal immunity. Age Ageing. 1991, 20 (1): 33-36. 10.1093/ageing/20.1.33.PubMed Penn ND, Purkins L, Kelleher J, Heatley RV, Mascie-Taylor BH: Ageing and duodenal mucosal immunity. Age Ageing. 1991, 20 (1): 33-36. 10.1093/ageing/20.1.33.PubMed
31.
go back to reference Senda S, Cheng E, Kawanishi H: Aging-associated changes in murine intestinal immunoglobulin A and M secretions. Scand J Immunol. 1988, 27 (2): 157-164. 10.1111/j.1365-3083.1988.tb02334.x.PubMed Senda S, Cheng E, Kawanishi H: Aging-associated changes in murine intestinal immunoglobulin A and M secretions. Scand J Immunol. 1988, 27 (2): 157-164. 10.1111/j.1365-3083.1988.tb02334.x.PubMed
32.
go back to reference Thoreux K, Owen RL, Schmucker DL: Intestinal lymphocyte number, migration and antibody secretion in young and old rats. Immunology. 2000, 101 (1): 161-167. 10.1046/j.1365-2567.2000.00095.x.PubMedCentralPubMed Thoreux K, Owen RL, Schmucker DL: Intestinal lymphocyte number, migration and antibody secretion in young and old rats. Immunology. 2000, 101 (1): 161-167. 10.1046/j.1365-2567.2000.00095.x.PubMedCentralPubMed
33.
go back to reference Schmucker DL: Intestinal mucosal immunosenescence in rats. Exp Gerontol. 2002, 37 (2-3): 197-203. 10.1016/S0531-5565(01)00184-X.PubMed Schmucker DL: Intestinal mucosal immunosenescence in rats. Exp Gerontol. 2002, 37 (2-3): 197-203. 10.1016/S0531-5565(01)00184-X.PubMed
34.
go back to reference Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T: Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science. 2002, 298 (5597): 1424-1427. 10.1126/science.1077336.PubMed Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T: Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science. 2002, 298 (5597): 1424-1427. 10.1126/science.1077336.PubMed
35.
go back to reference McDonald LC, Owings M, Jernigan DB: Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006, 12 (3): 409-415.PubMedCentralPubMed McDonald LC, Owings M, Jernigan DB: Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006, 12 (3): 409-415.PubMedCentralPubMed
36.
go back to reference Warny M, Vaerman JP, Avesani V, Delmee M: Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun. 1994, 62 (2): 384-389.PubMedCentralPubMed Warny M, Vaerman JP, Avesani V, Delmee M: Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun. 1994, 62 (2): 384-389.PubMedCentralPubMed
37.
go back to reference Schmucker DL, Daniels CK, Wang RK, Smith K: Mucosal immune response to cholera toxin in ageing rats. I. Antibody and antibody-containing cell response. Immunology. 1988, 64 (4): 691-695.PubMedCentralPubMed Schmucker DL, Daniels CK, Wang RK, Smith K: Mucosal immune response to cholera toxin in ageing rats. I. Antibody and antibody-containing cell response. Immunology. 1988, 64 (4): 691-695.PubMedCentralPubMed
38.
go back to reference Taylor LD, Daniels CK, Schmucker DL: Ageing compromises gastrointestinal mucosal immune response in the rhesus monkey. Immunology. 1992, 75 (4): 614-618.PubMedCentralPubMed Taylor LD, Daniels CK, Schmucker DL: Ageing compromises gastrointestinal mucosal immune response in the rhesus monkey. Immunology. 1992, 75 (4): 614-618.PubMedCentralPubMed
39.
go back to reference Enioutina EY, Visic VD, Daynes RA: Enhancement of common mucosal immunity in aged mice following their supplementation with various antioxidants. Vaccine. 2000, 18 (22): 2381-2393. 10.1016/S0264-410X(00)00008-6.PubMed Enioutina EY, Visic VD, Daynes RA: Enhancement of common mucosal immunity in aged mice following their supplementation with various antioxidants. Vaccine. 2000, 18 (22): 2381-2393. 10.1016/S0264-410X(00)00008-6.PubMed
40.
go back to reference Chaplin DD, Fu Y: Cytokine regulation of secondary lymphoid organ development. Curr Opin Immunol. 1998, 10 (3): 289-297. 10.1016/S0952-7915(98)80167-2.PubMed Chaplin DD, Fu Y: Cytokine regulation of secondary lymphoid organ development. Curr Opin Immunol. 1998, 10 (3): 289-297. 10.1016/S0952-7915(98)80167-2.PubMed
41.
go back to reference De Togni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J: Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994, 264 (5159): 703-707. 10.1126/science.8171322.PubMed De Togni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J: Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994, 264 (5159): 703-707. 10.1126/science.8171322.PubMed
42.
go back to reference Rennert PD, Browning JL, Hochman PS: Selective disruption of lymphotoxin ligands reveals a novel set of mucosal lymph nodes and unique effects on lymph node cellular organization. Int Immunol. 1997, 9 (11): 1627-1639. 10.1093/intimm/9.11.1627.PubMed Rennert PD, Browning JL, Hochman PS: Selective disruption of lymphotoxin ligands reveals a novel set of mucosal lymph nodes and unique effects on lymph node cellular organization. Int Immunol. 1997, 9 (11): 1627-1639. 10.1093/intimm/9.11.1627.PubMed
43.
go back to reference Rennert PD, Browning JL, Mebius R, Mackay F, Hochman PS: Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs. J Exp Med. 1996, 184 (5): 1999-2006. 10.1084/jem.184.5.1999.PubMed Rennert PD, Browning JL, Mebius R, Mackay F, Hochman PS: Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs. J Exp Med. 1996, 184 (5): 1999-2006. 10.1084/jem.184.5.1999.PubMed
44.
go back to reference Fujimura Y, Kamoi R, Iida M: Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry. Gut. 1996, 38 (5): 724-732. 10.1136/gut.38.5.724.PubMedCentralPubMed Fujimura Y, Kamoi R, Iida M: Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry. Gut. 1996, 38 (5): 724-732. 10.1136/gut.38.5.724.PubMedCentralPubMed
45.
go back to reference Lockhart-Mummery HE, Morson BC: Crohn's disease (regional enteritis) of the large intestine and its distinction from ulcerative colitis. Gut. 1960, 1: 87-105. 10.1136/gut.1.2.87.PubMedCentralPubMed Lockhart-Mummery HE, Morson BC: Crohn's disease (regional enteritis) of the large intestine and its distinction from ulcerative colitis. Gut. 1960, 1: 87-105. 10.1136/gut.1.2.87.PubMedCentralPubMed
46.
go back to reference Tanaka Y, Imai T, Baba M, Ishikawa I, Uehira M, Nomiyama H, Yoshie O: Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans. Eur J Immunol. 1999, 29 (2): 633-642. 10.1002/(SICI)1521-4141(199902)29:02<633::AID-IMMU633>3.0.CO;2-I.PubMed Tanaka Y, Imai T, Baba M, Ishikawa I, Uehira M, Nomiyama H, Yoshie O: Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans. Eur J Immunol. 1999, 29 (2): 633-642. 10.1002/(SICI)1521-4141(199902)29:02<633::AID-IMMU633>3.0.CO;2-I.PubMed
47.
go back to reference Izadpanah A, Dwinell MB, Eckmann L, Varki NM, Kagnoff MF: Regulated MIP-3alpha/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. Am J Physiol Gastrointest Liver Physiol. 2001, 280 (4): G710-719.PubMed Izadpanah A, Dwinell MB, Eckmann L, Varki NM, Kagnoff MF: Regulated MIP-3alpha/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. Am J Physiol Gastrointest Liver Physiol. 2001, 280 (4): G710-719.PubMed
48.
go back to reference Kaser A, Ludwiczek O, Holzmann S, Moschen AR, Weiss G, Enrich B, Graziadei I, Dunzendorfer S, Wiedermann CJ, Murzl E: Increased expression of CCL20 in human inflammatory bowel disease. J Clin Immunol. 2004, 24 (1): 74-85. 10.1023/B:JOCI.0000018066.46279.6b.PubMed Kaser A, Ludwiczek O, Holzmann S, Moschen AR, Weiss G, Enrich B, Graziadei I, Dunzendorfer S, Wiedermann CJ, Murzl E: Increased expression of CCL20 in human inflammatory bowel disease. J Clin Immunol. 2004, 24 (1): 74-85. 10.1023/B:JOCI.0000018066.46279.6b.PubMed
49.
go back to reference Kwon JH, Keates S, Bassani L, Mayer LF, Keates AC: Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut. 2002, 51 (6): 818-826. 10.1136/gut.51.6.818.PubMedCentralPubMed Kwon JH, Keates S, Bassani L, Mayer LF, Keates AC: Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut. 2002, 51 (6): 818-826. 10.1136/gut.51.6.818.PubMedCentralPubMed
50.
go back to reference Bowman EP, Campbell JJ, Soler D, Dong Z, Manlongat N, Picarella D, Hardy RR, Butcher EC: Developmental switches in chemokine response profiles during B cell differentiation and maturation. J Exp Med. 2000, 191 (8): 1303-1318. 10.1084/jem.191.8.1303.PubMedCentralPubMed Bowman EP, Campbell JJ, Soler D, Dong Z, Manlongat N, Picarella D, Hardy RR, Butcher EC: Developmental switches in chemokine response profiles during B cell differentiation and maturation. J Exp Med. 2000, 191 (8): 1303-1318. 10.1084/jem.191.8.1303.PubMedCentralPubMed
51.
go back to reference Ishimoto Y, Tomiyama-Miyaji C, Watanabe H, Yokoyama H, Ebe K, Tsubata S, Aoyagi Y, Abo T: Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially natural killer T cells, double-positive CD4+ CD8+ cells and B220+ T cells, in mice. Immunology. 2004, 113 (3): 371-377. 10.1111/j.1365-2567.2004.01961.x.PubMedCentralPubMed Ishimoto Y, Tomiyama-Miyaji C, Watanabe H, Yokoyama H, Ebe K, Tsubata S, Aoyagi Y, Abo T: Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially natural killer T cells, double-positive CD4+ CD8+ cells and B220+ T cells, in mice. Immunology. 2004, 113 (3): 371-377. 10.1111/j.1365-2567.2004.01961.x.PubMedCentralPubMed
52.
go back to reference Yamada K, Kimura Y, Nishimura H, Namii Y, Murase M, Yoshikai Y: Characterization of CD4+ CD8alphaalpha+ and CD4-CD8alphaalpha+ intestinal intraepithelial lymphocytes in rats. Int Immunol. 1999, 11 (1): 21-28. 10.1093/intimm/11.1.21.PubMed Yamada K, Kimura Y, Nishimura H, Namii Y, Murase M, Yoshikai Y: Characterization of CD4+ CD8alphaalpha+ and CD4-CD8alphaalpha+ intestinal intraepithelial lymphocytes in rats. Int Immunol. 1999, 11 (1): 21-28. 10.1093/intimm/11.1.21.PubMed
53.
go back to reference Jimenez E, Sacedon R, Vicente A, Hernandez-Lopez C, Zapata AG, Varas A: Rat peripheral CD4+CD8+ T lymphocytes are partially immunocompetent thymus-derived cells that undergo post-thymic maturation to become functionally mature CD4+ T lymphocytes. J Immunol. 2002, 168 (10): 5005-5013.PubMed Jimenez E, Sacedon R, Vicente A, Hernandez-Lopez C, Zapata AG, Varas A: Rat peripheral CD4+CD8+ T lymphocytes are partially immunocompetent thymus-derived cells that undergo post-thymic maturation to become functionally mature CD4+ T lymphocytes. J Immunol. 2002, 168 (10): 5005-5013.PubMed
54.
go back to reference Colombatti A, Doliana R, Schiappacassi M, Argentini C, Tonutti E, Feruglio C, Sala P: Age-related persistent clonal expansions of CD28(-) cells: phenotypic and molecular TCR analysis reveals both CD4(+) and CD4(+)CD8(+) cells with identical CDR3 sequences. Clin Immunol Immunopathol. 1998, 89 (1): 61-70. 10.1006/clin.1998.4580.PubMed Colombatti A, Doliana R, Schiappacassi M, Argentini C, Tonutti E, Feruglio C, Sala P: Age-related persistent clonal expansions of CD28(-) cells: phenotypic and molecular TCR analysis reveals both CD4(+) and CD4(+)CD8(+) cells with identical CDR3 sequences. Clin Immunol Immunopathol. 1998, 89 (1): 61-70. 10.1006/clin.1998.4580.PubMed
55.
go back to reference Laux I, Khoshnan A, Tindell C, Bae D, Zhu X, June CH, Effros RB, Nel A: Response differences between human CD4(+) and CD8(+) T-cells during CD28 costimulation: implications for immune cell-based therapies and studies related to the expansion of double-positive T-cells during aging. Clin Immunol. 2000, 96 (3): 187-197. 10.1006/clim.2000.4902.PubMed Laux I, Khoshnan A, Tindell C, Bae D, Zhu X, June CH, Effros RB, Nel A: Response differences between human CD4(+) and CD8(+) T-cells during CD28 costimulation: implications for immune cell-based therapies and studies related to the expansion of double-positive T-cells during aging. Clin Immunol. 2000, 96 (3): 187-197. 10.1006/clim.2000.4902.PubMed
56.
go back to reference Kenny E, Mason D, Saoudi A, Pombo A, Ramirez F: CD8 alpha is an activation marker for a subset of peripheral CD4 T cells. Eur J Immunol. 2004, 34 (5): 1262-1271. 10.1002/eji.200324363.PubMed Kenny E, Mason D, Saoudi A, Pombo A, Ramirez F: CD8 alpha is an activation marker for a subset of peripheral CD4 T cells. Eur J Immunol. 2004, 34 (5): 1262-1271. 10.1002/eji.200324363.PubMed
57.
go back to reference Hori T, Paliard X, de Waal Malefijt R, Ranes M, Spits H: Comparative analysis of CD8 expressed on mature CD4+ CD8+ T cell clones cultured with IL-4 and that on CD8+ T cell clones: implication for functional significance of CD8 beta. Int Immunol. 1991, 3 (7): 737-741. 10.1093/intimm/3.7.737.PubMed Hori T, Paliard X, de Waal Malefijt R, Ranes M, Spits H: Comparative analysis of CD8 expressed on mature CD4+ CD8+ T cell clones cultured with IL-4 and that on CD8+ T cell clones: implication for functional significance of CD8 beta. Int Immunol. 1991, 3 (7): 737-741. 10.1093/intimm/3.7.737.PubMed
58.
go back to reference Akari H, Terao K, Murayama Y, Nam KH, Yoshikawa Y: Peripheral blood CD4+CD8+ lymphocytes in cynomolgus monkeys are of resting memory T lineage. Int Immunol. 1997, 9 (4): 591-597. 10.1093/intimm/9.4.591.PubMed Akari H, Terao K, Murayama Y, Nam KH, Yoshikawa Y: Peripheral blood CD4+CD8+ lymphocytes in cynomolgus monkeys are of resting memory T lineage. Int Immunol. 1997, 9 (4): 591-597. 10.1093/intimm/9.4.591.PubMed
59.
go back to reference Parel Y, Chizzolini C: CD4+ CD8+ double positive (DP) T cells in health and disease. Autoimmun Rev. 2004, 3 (3): 215-220. 10.1016/j.autrev.2003.09.001.PubMed Parel Y, Chizzolini C: CD4+ CD8+ double positive (DP) T cells in health and disease. Autoimmun Rev. 2004, 3 (3): 215-220. 10.1016/j.autrev.2003.09.001.PubMed
60.
go back to reference Lee WW, Nam KH, Terao K, Akari H, Yoshikawa Y: Age-related increase of peripheral CD4+ CD8+ double-positive T lymphocytes in cynomolgus monkeys: longitudinal study in relation to thymic involution. Immunology. 2003, 109 (2): 217-225. 10.1046/j.1365-2567.2003.01646.x.PubMedCentralPubMed Lee WW, Nam KH, Terao K, Akari H, Yoshikawa Y: Age-related increase of peripheral CD4+ CD8+ double-positive T lymphocytes in cynomolgus monkeys: longitudinal study in relation to thymic involution. Immunology. 2003, 109 (2): 217-225. 10.1046/j.1365-2567.2003.01646.x.PubMedCentralPubMed
61.
go back to reference Ebersole JL, Smith DJ, Taubman MA: Secretory immune responses in ageing rats. I. Immunoglobulin levels. Immunology. 1985, 56 (2): 345-350.PubMedCentralPubMed Ebersole JL, Smith DJ, Taubman MA: Secretory immune responses in ageing rats. I. Immunoglobulin levels. Immunology. 1985, 56 (2): 345-350.PubMedCentralPubMed
62.
go back to reference Gibson KL, Wu YC, Barnett Y, Duggan O, Vaughan R, Kondeatis E, Nilsson BO, Wikby A, Kipling D, Dunn-Walters DK: B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell. 2009, 8 (1): 18-25. 10.1111/j.1474-9726.2008.00443.x.PubMedCentralPubMed Gibson KL, Wu YC, Barnett Y, Duggan O, Vaughan R, Kondeatis E, Nilsson BO, Wikby A, Kipling D, Dunn-Walters DK: B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell. 2009, 8 (1): 18-25. 10.1111/j.1474-9726.2008.00443.x.PubMedCentralPubMed
63.
go back to reference Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, Blomberg BB: B cells and aging: molecules and mechanisms. Trends Immunol. 2009, 30 (7): 313-318. 10.1016/j.it.2009.04.005.PubMedCentralPubMed Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, Blomberg BB: B cells and aging: molecules and mechanisms. Trends Immunol. 2009, 30 (7): 313-318. 10.1016/j.it.2009.04.005.PubMedCentralPubMed
64.
go back to reference Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivanov II, Itoh K, Littman DR, Fagarasan S: Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity. 2008, 29 (2): 261-271. 10.1016/j.immuni.2008.05.014.PubMed Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivanov II, Itoh K, Littman DR, Fagarasan S: Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity. 2008, 29 (2): 261-271. 10.1016/j.immuni.2008.05.014.PubMed
65.
go back to reference Stoel M, Jiang HQ, van Diemen CC, Bun JC, Dammers PM, Thurnheer MC, Kroese FG, Cebra JJ, Bos NA: Restricted IgA repertoire in both B-1 and B-2 cell-derived gut plasmablasts. J Immunol. 2005, 174 (2): 1046-1054.PubMed Stoel M, Jiang HQ, van Diemen CC, Bun JC, Dammers PM, Thurnheer MC, Kroese FG, Cebra JJ, Bos NA: Restricted IgA repertoire in both B-1 and B-2 cell-derived gut plasmablasts. J Immunol. 2005, 174 (2): 1046-1054.PubMed
Metadata
Title
Aging impacts isolated lymphoid follicle development and function
Authors
Keely G McDonald
Matthew R Leach
Conway Huang
Caihong Wang
Rodney D Newberry
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2011
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/1742-4933-8-1

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