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Published in: International Journal of Colorectal Disease 9/2010

01-09-2010 | Original Article

The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in γδ T cells in large intestinal mucosa

Authors: Yuefang Ye, Xi Jin, Min Yue, Shaohua Chen, Chaohui Yu, Youming Li

Published in: International Journal of Colorectal Disease | Issue 9/2010

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Abstract

Backgrounds and aims

Oral tolerance has previously been shown effective in preventing several immune-mediated disorders in animal models. The aims of this study were to investigate the effect of oral colitis-extracted proteins (CEP) on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice and to explore the relative role of the intestinal mucosal γδ T cells.

Methods

The effect of five low oral doses of CEP on colitis was evaluated by clinical manifestation and histological lesions. Serum cytokines were measured by enzyme-linked immunosorbent assay. The percentages of the intestinal mucosal γδ T cells were evaluated by flow cytometry.

Results

CEP-fed colitis mice showed less severe symptoms and histological injury than bovine serum albumin (BSA)-fed control mice. Tolerized mice developed an increase in TGF-β1 and no change in IFN-γ serum levels. Increases in TCRγδ+ T cells and CD8α+TCRγδ+ T cells in small intestinal mucosal lymphocytes and no quantitative change in large intestinal mucosal lymphocytes were demonstrated in colitis mice compared to untreated mice. The proportions of TCRγδ+ T cells and CD8α+TCRγδ+ T cells in large intestinal mucosal lymphocytes from CEP-fed colitis mice were significantly higher compared to BSA-fed controls. The disease activity index negatively correlated with the percentages of large intestinal mucosal γδ T cells. Furthermore, mucosal repair in repair-period mice was also accompanied by increases in TCRγδ+ T cells and CD8α+TCRγδ+ T cells in large intestinal mucosal lymphocytes.

Conclusion

Improvement of DSS-induced colitis that resulted from oral administration of colitis-extracted proteins is associated with an increase in γδ T cells in large intestinal mucosa.
Literature
2.
go back to reference Hyun JG, Barrett TA (2006) Oral tolerance therapy in inflammatory bowel disease. Am J Gastroenterol 101:569–571CrossRefPubMed Hyun JG, Barrett TA (2006) Oral tolerance therapy in inflammatory bowel disease. Am J Gastroenterol 101:569–571CrossRefPubMed
3.
go back to reference Whitacre CC, Gienapp IE, Meyer A, Cox KL, Javed N (1996) Oral tolerance in experimental autoimmune encephalomyelitis. Ann N Y Acad Sci 778:217–227CrossRefPubMed Whitacre CC, Gienapp IE, Meyer A, Cox KL, Javed N (1996) Oral tolerance in experimental autoimmune encephalomyelitis. Ann N Y Acad Sci 778:217–227CrossRefPubMed
4.
go back to reference von Herrath MG, Dyrberg T, Oldstone MB (1996) Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice. J Clin Invest 98:1324–1331CrossRef von Herrath MG, Dyrberg T, Oldstone MB (1996) Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice. J Clin Invest 98:1324–1331CrossRef
5.
go back to reference Ilan Y, Gotsman I, Pines M, Beinart R, Zeira M, Ohana M, Rabbani E, Engelhardt D, Nagler A (2000) Induction of oral tolerance in splenocyte recipients toward pretransplant antigens ameliorates chronic graft versus host disease in a murine model. Blood 95:3613–3619PubMed Ilan Y, Gotsman I, Pines M, Beinart R, Zeira M, Ohana M, Rabbani E, Engelhardt D, Nagler A (2000) Induction of oral tolerance in splenocyte recipients toward pretransplant antigens ameliorates chronic graft versus host disease in a murine model. Blood 95:3613–3619PubMed
6.
go back to reference Trentham DE (1998) Oral tolerization as a treatment of rheumatoid arthritis. Rheum Dis Clin North Am 24:525–536CrossRefPubMed Trentham DE (1998) Oral tolerization as a treatment of rheumatoid arthritis. Rheum Dis Clin North Am 24:525–536CrossRefPubMed
7.
go back to reference Ilan Y, Weksler-Zangen S, Ben-Horin S, Diment J, Sauter B, Rabbani E, Engelhardt D, Chowdhury NR, Chowdhury JR, Goldin E (2000) Treatment of experimental colitis by oral tolerance induction: a central role for suppressor lymphocytes. Am J Gastroenterol 95:966–973CrossRefPubMed Ilan Y, Weksler-Zangen S, Ben-Horin S, Diment J, Sauter B, Rabbani E, Engelhardt D, Chowdhury NR, Chowdhury JR, Goldin E (2000) Treatment of experimental colitis by oral tolerance induction: a central role for suppressor lymphocytes. Am J Gastroenterol 95:966–973CrossRefPubMed
8.
go back to reference Gotsman I, Shlomai A, Alper R, Rabbani E, Engelhardt D, Ilan Y (2001) Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of preexisting immunity and surrogate antigen bystander effect. J Pharmacol Exp Ther 297:926–932PubMed Gotsman I, Shlomai A, Alper R, Rabbani E, Engelhardt D, Ilan Y (2001) Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of preexisting immunity and surrogate antigen bystander effect. J Pharmacol Exp Ther 297:926–932PubMed
9.
go back to reference Dasgupta A, Kesari KV, Ramaswamy KK, Amenta PS, Das KM (2001) Oral administration of unmodified colonic but not small intestinal antigens protects rats from hapten-induced colitis. Clin Exp Immunol 125:41–47CrossRefPubMed Dasgupta A, Kesari KV, Ramaswamy KK, Amenta PS, Das KM (2001) Oral administration of unmodified colonic but not small intestinal antigens protects rats from hapten-induced colitis. Clin Exp Immunol 125:41–47CrossRefPubMed
10.
go back to reference Israeli E, Goldin E, Shibolet O, Klein A, Hemed N, Engelhardt D, Rabbani E, Ilan Y (2005) Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: results of a phase I clinical trial. World J Gastroenterol 11:3105–3111PubMed Israeli E, Goldin E, Shibolet O, Klein A, Hemed N, Engelhardt D, Rabbani E, Ilan Y (2005) Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: results of a phase I clinical trial. World J Gastroenterol 11:3105–3111PubMed
11.
go back to reference Margalit M, Israeli E, Shibolet O, Zigmond E, Klein A, Hemed N, Donegan JJ, Rabbani E, Goldin E, Ilan Y (2006) A double-blind clinical trial for treatment of Crohn's disease by oral administration of Alequel, a mixture of autologous colon-extracted proteins: a patient-tailored approach. Am J Gastroenterol 101:561–568CrossRefPubMed Margalit M, Israeli E, Shibolet O, Zigmond E, Klein A, Hemed N, Donegan JJ, Rabbani E, Goldin E, Ilan Y (2006) A double-blind clinical trial for treatment of Crohn's disease by oral administration of Alequel, a mixture of autologous colon-extracted proteins: a patient-tailored approach. Am J Gastroenterol 101:561–568CrossRefPubMed
12.
go back to reference Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694–702PubMed Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694–702PubMed
13.
go back to reference Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249PubMed Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249PubMed
14.
go back to reference Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385–391CrossRefPubMed Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385–391CrossRefPubMed
15.
go back to reference Kunisawa J, Takahashi I, Kiyono H (2007) Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine. Immunol Rev 215:136–153CrossRefPubMed Kunisawa J, Takahashi I, Kiyono H (2007) Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine. Immunol Rev 215:136–153CrossRefPubMed
16.
go back to reference Cheroutre H (2005) IELs: enforcing law and order in the court of the intestinal epithelium. Immunol Rev 206:114–131CrossRefPubMed Cheroutre H (2005) IELs: enforcing law and order in the court of the intestinal epithelium. Immunol Rev 206:114–131CrossRefPubMed
17.
go back to reference Komano H, Fujiura Y, Kawaguchi M, Matsumoto S, Hashimoto Y, Obana S, Mombaerts P, Tonegawa S, Yamamoto H, Itohara S (1995) Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A 92:6147–6151CrossRefPubMed Komano H, Fujiura Y, Kawaguchi M, Matsumoto S, Hashimoto Y, Obana S, Mombaerts P, Tonegawa S, Yamamoto H, Itohara S (1995) Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A 92:6147–6151CrossRefPubMed
18.
go back to reference Dalton JE, Cruickshank SM, Egan CE, Mears R, Newton DJ, Andrew EM, Lawrence B, Howell G, Else KJ, Gubbels MJ, Striepen B, Smith JE, White SJ, Carding SR (2006) Intraepithelial gammadelta + lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 131:818–829CrossRefPubMed Dalton JE, Cruickshank SM, Egan CE, Mears R, Newton DJ, Andrew EM, Lawrence B, Howell G, Else KJ, Gubbels MJ, Striepen B, Smith JE, White SJ, Carding SR (2006) Intraepithelial gammadelta + lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 131:818–829CrossRefPubMed
19.
go back to reference Yang H, Antony PA, Wildhaber BE, Teitelbaum DH (2004) Intestinal intraepithelial lymphocyte gamma delta-T cell-derived keratinocyte growth factor modulates epithelial growth in the mouse. J Immunol 172:4151–4158PubMed Yang H, Antony PA, Wildhaber BE, Teitelbaum DH (2004) Intestinal intraepithelial lymphocyte gamma delta-T cell-derived keratinocyte growth factor modulates epithelial growth in the mouse. J Immunol 172:4151–4158PubMed
20.
go back to reference Mengel J, Cardillo F, Aroeira LS, Williams O, Russo M, Vaz NM (1995) Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice. Immunol Lett 48:97–102CrossRefPubMed Mengel J, Cardillo F, Aroeira LS, Williams O, Russo M, Vaz NM (1995) Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice. Immunol Lett 48:97–102CrossRefPubMed
21.
go back to reference Fujihashi K, Dohi T, Kweon MN, McGhee JR, Koga T, Cooper MD, Tonegawa S, Kiyono H (1999) gammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion. Int Immunol 11:1907–1916CrossRefPubMed Fujihashi K, Dohi T, Kweon MN, McGhee JR, Koga T, Cooper MD, Tonegawa S, Kiyono H (1999) gammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion. Int Immunol 11:1907–1916CrossRefPubMed
22.
go back to reference Ke Y, Pearce K, Lake JP, Ziegler HK, Kapp JA (1997) Gamma delta T lymphocytes regulate the induction and maintenance of oral tolerance. J Immunol 158:3610–3618PubMed Ke Y, Pearce K, Lake JP, Ziegler HK, Kapp JA (1997) Gamma delta T lymphocytes regulate the induction and maintenance of oral tolerance. J Immunol 158:3610–3618PubMed
23.
go back to reference Locke NR, Stankovic S, Funda DP, Harrison LC (2006) TCR gamma delta intraepithelial lymphocytes are required for self-tolerance. J Immunol 176:6553–6559PubMed Locke NR, Stankovic S, Funda DP, Harrison LC (2006) TCR gamma delta intraepithelial lymphocytes are required for self-tolerance. J Immunol 176:6553–6559PubMed
24.
go back to reference Kapp JA, Kapp LM, McKenna KC, Lake JP (2004) gammadelta T-cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses ex vivo. Immunology 111:155–164CrossRefPubMed Kapp JA, Kapp LM, McKenna KC, Lake JP (2004) gammadelta T-cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses ex vivo. Immunology 111:155–164CrossRefPubMed
25.
go back to reference Kawaguchi-Miyashita M, Shimada S, Matsuoka Y, Ohwaki M, Nanno M (2000) Activation of T-cell receptor-gammadelta + cells in the intestinal epithelia of KN6 transgenic mice. Immunology 101:38–45CrossRefPubMed Kawaguchi-Miyashita M, Shimada S, Matsuoka Y, Ohwaki M, Nanno M (2000) Activation of T-cell receptor-gammadelta + cells in the intestinal epithelia of KN6 transgenic mice. Immunology 101:38–45CrossRefPubMed
26.
go back to reference Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, Raulet DH, Lanier LL, Groh V, Spies T, Ebert EC, Green PH, Jabri B (2004) Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21:357–366CrossRefPubMed Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, Raulet DH, Lanier LL, Groh V, Spies T, Ebert EC, Green PH, Jabri B (2004) Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21:357–366CrossRefPubMed
27.
go back to reference Nanno M, Kanari Y, Naito T, Inoue N, Hisamatsu T, Chinen H, Sugimoto K, Shimomura Y, Yamagishi H, Shiohara T, Ueha S, Matsushima K, Suematsu M, Mizoguchi A, Hibi T, Bhan AK, Ishikawa H (2008) Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice. Gastroenterology 134:481–490CrossRefPubMed Nanno M, Kanari Y, Naito T, Inoue N, Hisamatsu T, Chinen H, Sugimoto K, Shimomura Y, Yamagishi H, Shiohara T, Ueha S, Matsushima K, Suematsu M, Mizoguchi A, Hibi T, Bhan AK, Ishikawa H (2008) Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice. Gastroenterology 134:481–490CrossRefPubMed
28.
go back to reference Nanno M, Shiohara T, Yamamoto H, Kawakami K, Ishikawa H (2007) gammadelta T cells: firefighters or fire boosters in the front lines of inflammatory responses. Immunol Rev 215:103–113CrossRefPubMed Nanno M, Shiohara T, Yamamoto H, Kawakami K, Ishikawa H (2007) gammadelta T cells: firefighters or fire boosters in the front lines of inflammatory responses. Immunol Rev 215:103–113CrossRefPubMed
29.
go back to reference Kuhl AA, Pawlowski NN, Grollich K, Loddenkemper C, Zeitz M, Hoffmann JC (2007) Aggravation of intestinal inflammation by depletion/deficiency of gammadelta T cells in different types of IBD animal models. J Leukoc Biol 81:168–175CrossRefPubMed Kuhl AA, Pawlowski NN, Grollich K, Loddenkemper C, Zeitz M, Hoffmann JC (2007) Aggravation of intestinal inflammation by depletion/deficiency of gammadelta T cells in different types of IBD animal models. J Leukoc Biol 81:168–175CrossRefPubMed
30.
go back to reference Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R (2002) Protection of the intestinal mucosa by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A 99:14338–14343CrossRefPubMed Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R (2002) Protection of the intestinal mucosa by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A 99:14338–14343CrossRefPubMed
31.
go back to reference Inagaki-Ohara K, Chinen T, Matsuzaki G, Sasaki A, Sakamoto Y, Hiromatsu K, Nakamura-Uchiyama F, Nawa Y, Yoshimura A (2004) Mucosal T cells bearing TCRgammadelta play a protective role in intestinal inflammation. J Immunol 173:1390–1398PubMed Inagaki-Ohara K, Chinen T, Matsuzaki G, Sasaki A, Sakamoto Y, Hiromatsu K, Nakamura-Uchiyama F, Nawa Y, Yoshimura A (2004) Mucosal T cells bearing TCRgammadelta play a protective role in intestinal inflammation. J Immunol 173:1390–1398PubMed
32.
go back to reference Tsuchiya T, Fukuda S, Hamada H, Nakamura A, Kohama Y, Ishikawa H, Tsujikawa K, Yamamoto H (2003) Role of gamma delta T cells in the inflammatory response of experimental colitis mice. J Immunol 171:5507–5513PubMed Tsuchiya T, Fukuda S, Hamada H, Nakamura A, Kohama Y, Ishikawa H, Tsujikawa K, Yamamoto H (2003) Role of gamma delta T cells in the inflammatory response of experimental colitis mice. J Immunol 171:5507–5513PubMed
33.
go back to reference McVay LD, Li B, Biancaniello R, Creighton MA, Bachwich D, Lichtenstein G, Rombeau JL, Carding SR (1997) Changes in human mucosal gamma delta T cell repertoire and function associated with the disease process in inflammatory bowel disease. Mol Med 3:183–203PubMed McVay LD, Li B, Biancaniello R, Creighton MA, Bachwich D, Lichtenstein G, Rombeau JL, Carding SR (1997) Changes in human mucosal gamma delta T cell repertoire and function associated with the disease process in inflammatory bowel disease. Mol Med 3:183–203PubMed
34.
go back to reference Trejdosiewicz LK, Calabrese A, Smart CJ, Oakes DJ, Howdle PD, Crabtree JE, Losowsky MS, Lancaster F, Boylston AW (1991) Gamma delta T cell receptor-positive cells of the human gastrointestinal mucosa: occurrence and V region gene expression in Heliobacter pylori-associated gastritis, coeliac disease and inflammatory bowel disease. Clin Exp Immunol 84:440–444PubMed Trejdosiewicz LK, Calabrese A, Smart CJ, Oakes DJ, Howdle PD, Crabtree JE, Losowsky MS, Lancaster F, Boylston AW (1991) Gamma delta T cell receptor-positive cells of the human gastrointestinal mucosa: occurrence and V region gene expression in Heliobacter pylori-associated gastritis, coeliac disease and inflammatory bowel disease. Clin Exp Immunol 84:440–444PubMed
35.
go back to reference Fukushima K, Masuda T, Ohtani H, Sasaki I, Funayama Y, Matsuno S, Nagura H (1991) Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease. Gastroenterology 101:670–678PubMed Fukushima K, Masuda T, Ohtani H, Sasaki I, Funayama Y, Matsuno S, Nagura H (1991) Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease. Gastroenterology 101:670–678PubMed
36.
go back to reference Resendiz-Albor AA, Esquivel R, Lopez-Revilla R, Verdin L, Moreno-Fierros L (2005) Striking phenotypic and functional differences in lamina propria lymphocytes from the large and small intestine of mice. Life Sci 76:2783–2803CrossRefPubMed Resendiz-Albor AA, Esquivel R, Lopez-Revilla R, Verdin L, Moreno-Fierros L (2005) Striking phenotypic and functional differences in lamina propria lymphocytes from the large and small intestine of mice. Life Sci 76:2783–2803CrossRefPubMed
37.
go back to reference Neurath MF, Fuss I, Kelsall BL, Presky DH, Waegell W, Strober W (1996) Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance. J Exp Med 183:2605–2616CrossRefPubMed Neurath MF, Fuss I, Kelsall BL, Presky DH, Waegell W, Strober W (1996) Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance. J Exp Med 183:2605–2616CrossRefPubMed
38.
go back to reference Elson CO, Beagley KW, Sharmanov AT, Fujihashi K, Kiyono H, Tennyson GS, Cong Y, Black CA, Ridwan BW, McGhee JR (1996) Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J Immunol 157:2174–2185PubMed Elson CO, Beagley KW, Sharmanov AT, Fujihashi K, Kiyono H, Tennyson GS, Cong Y, Black CA, Ridwan BW, McGhee JR (1996) Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J Immunol 157:2174–2185PubMed
39.
go back to reference Dasgupta A, Ramaswamy K, Giraldo J, Taniguchi M, Amenta PS, Das KM (2001) Colon epithelial cellular protein induces oral tolerance in the experimental model of colitis by trinitrobenzene sulfonic acid. J Lab Clin Med 138:257–269CrossRefPubMed Dasgupta A, Ramaswamy K, Giraldo J, Taniguchi M, Amenta PS, Das KM (2001) Colon epithelial cellular protein induces oral tolerance in the experimental model of colitis by trinitrobenzene sulfonic acid. J Lab Clin Med 138:257–269CrossRefPubMed
40.
go back to reference Hoffmann JC, Pawlowski NN, Grollich K, Loddenkemper C, Zeitz M, Kuhl AA (2008) Gammadelta T lymphocytes: a new type of regulatory T cells suppressing murine 2, 4, 6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Int J Colorectal Dis 23:909–920CrossRefPubMed Hoffmann JC, Pawlowski NN, Grollich K, Loddenkemper C, Zeitz M, Kuhl AA (2008) Gammadelta T lymphocytes: a new type of regulatory T cells suppressing murine 2, 4, 6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Int J Colorectal Dis 23:909–920CrossRefPubMed
41.
go back to reference Ke Y, Kapp JA (1996) Oral antigen inhibits priming of CD8+ CTL, CD4+ T cells, and antibody responses while activating CD8+ suppressor T cells. J Immunol 156:916–921PubMed Ke Y, Kapp JA (1996) Oral antigen inhibits priming of CD8+ CTL, CD4+ T cells, and antibody responses while activating CD8+ suppressor T cells. J Immunol 156:916–921PubMed
42.
go back to reference Pomie C, Menager-Marcq I, van Meerwijk JP (2008) Murine CD8+ regulatory T lymphocytes: the new era. Hum Immunol 69:708–714CrossRefPubMed Pomie C, Menager-Marcq I, van Meerwijk JP (2008) Murine CD8+ regulatory T lymphocytes: the new era. Hum Immunol 69:708–714CrossRefPubMed
Metadata
Title
The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in γδ T cells in large intestinal mucosa
Authors
Yuefang Ye
Xi Jin
Min Yue
Shaohua Chen
Chaohui Yu
Youming Li
Publication date
01-09-2010
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 9/2010
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-010-0975-9

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