Top

BMC Neurology

Published in:

Open Access 01-12-2010 | Research article

Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica

Authors: Akiyuki Uzawa, Masahiro Mori, Sei Hayakawa, Saeko Masuda, Fumio Nomura, Satoshi Kuwabara

Published in: BMC Neurology | Issue 1/2010

Abstract

Background

The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO.

Methods

We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission.

Results

Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4⁺CD25⁺ and CD4⁺CD45RO⁺ was higher, while that of CD4⁺CC chemokine receptor (CCR)3⁺ (T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4⁺CXC chemokine receptors (CXCR)3⁺/CD4⁺CCR3⁺ (Th1/Th2) and CD8⁺CXCR3⁺/CD8⁺CCR4⁺ (T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8⁺CXCR3⁺ T cell (Tc1) and CD4⁺CXCR3⁺ T cell (Th1) decreased significantly during remission in MS patients (P < 0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC.

Conclusions

Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3⁺ T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.

Available only for authorised users

Luster AD: Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med. 1998, 338: 436-45. 10.1056/NEJM199802123380706.CrossRefPubMed

Sørensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM, Frederiksen JL, Ransohoff RM: Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest. 1999, 103: 807-15. 10.1172/JCI5150.CrossRefPubMedPubMedCentral

Balashov KE, Rottman JB, Weiner HL, Hancock WW: CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. Proc Natl Acad Sci USA. 1999, 96: 6873-8. 10.1073/pnas.96.12.6873.CrossRefPubMedPubMedCentral

Misu T, Onodera H, Fujihara K, Matsushima K, Yoshie O, Okita N, Takase S, Itoyama Y: Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis: imbalance of Th1/Th2-associated chemokine signaling. J Neuroimmunol. 2001, 114: 207-12. 10.1016/S0165-5728(00)00456-2.CrossRefPubMed

Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, Gray PW, Matsushima K, yoshie O: Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol. 1999, 11: 81-8. 10.1093/intimm/11.1.81.CrossRefPubMed

Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG: Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006, 66: 1485-9. 10.1212/01.wnl.0000216139.44259.74.CrossRefPubMed

Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR: IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005, 202: 473-7. 10.1084/jem.20050304.CrossRefPubMedPubMedCentral

Roemer SF, Parisi JE, Lennon VA, Benarroch EE, Lassmann H, Bruck W, Mandler RN, Weinshenker BG, Pittock SJ, Wingerchuk DM, Lucchinetti CF: Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain. 2007, 130: 1194-205. 10.1093/brain/awl371.CrossRefPubMed

Ito S, Mori M, Makino T, Hayakawa S, Kuwabara S: "Cloud-like enhancement" is a magnetic resonance imaging abnormality specific to neuromyelitis optica. Ann Neurol. 2009, 66: 425-8. 10.1002/ana.21753.CrossRefPubMed

10.

Ishizu T, Osoegawa M, Mei FJ, Kikuchi H, Tanaka M, Takakura Y, Minohara M, Murai H, Mihara F, Taniwaki T, Kira J: Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain. 2005, 128: 988-1002. 10.1093/brain/awh453.CrossRefPubMed

11.

Uzawa A, Mori M, Ito M, Uchida T, Hayakawa S, Masuda S, Kuwabara S: Markedly increased CSF interleukin-6 levels in neuromyelitis optica, but not in multiple sclerosis. J Neurol. 2009, 256: 2082-4. 10.1007/s00415-009-5274-4.CrossRefPubMed

12.

Uzawa A, Mori M, Hayakawa S, Masuda S, Kuwabara S: Different responses to interferon beta-1b treatment in patients with neuromyelitis optica and multiple sclerosis. Eur J Neurol. 2010, 17: 672-6. 10.1111/j.1468-1331.2009.02897.x.CrossRefPubMed

13.

Hayakawa S, Mori M, Okuta A, Kamegawa A, Fujiyoshi Y, Mitsuoka K, Ishibashi K, Sasaki S, Hattori T, Kuwabara S: Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay. J Neuroimmunol. 2008, 196: 181-7. 10.1016/j.jneuroim.2008.03.009.CrossRefPubMed

14.

McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS: Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001, 50: 121-7. 10.1002/ana.1032.CrossRefPubMed

15.

Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F: Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med. 1998, 187: 129-34. 10.1084/jem.187.1.129.CrossRefPubMedPubMedCentral

16.

Wu XM, Osoegawa M, Yamasaki K, Kawano Y, Ochi H, Horiuchi I, Minohara M, Ohyagi Y, Yamada T, Kira JI: Flow cytometric differentiation of Asian and Western types of multiple sclerosis, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and hyperIgEaemic myelitis by analyses of memory CD4 positive T cell subsets and NK cell subsets. J Neurol Sci. 2000, 177: 24-31. 10.1016/S0022-510X(00)00322-1.CrossRefPubMed

17.

Wang HY, Matsui M, Araya S, Onai N, Matsushima K, Saida T: Immune parameters associated with early treatment effects of high-dose intravenous methylprednisolone in multiple sclerosis. J Neurol Sci. 2003, 216: 61-6. 10.1016/S0022-510X(03)00214-4.CrossRefPubMed

18.

Kobayashi N, Kondo T, Takata H, Yokota S, Takiguchi M: Functional and phenotypic analysis of human memory CD8+ T cells expressing CXCR3. J Leukoc Biol. 2006, 80: 320-9. 10.1189/jlb.1205725.CrossRefPubMed

19.

Shi Z, Okuno Y, Rifa'i M, Endharti AT, Akane K, Isobe K, Suzuki H: Human CD8+CXCR3+ T cells have the same function as murine CD8+CD122+ Treg. Eur J Immunol. 2009, 39: 2106-19. 10.1002/eji.200939314.CrossRefPubMed

20.

Narikawa K, Misu T, Fujihara K, Nakashima I, Sato S, Itoyama Y: CSF chemokine levels in relapsing neuromyelitis optica and multiple sclerosis. J Neuroimmunol. 2004, 149: 182-6. 10.1016/j.jneuroim.2003.12.010.CrossRefPubMed

21.

Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC: Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010, 133: 349-61. 10.1093/brain/awp309.CrossRefPubMedPubMedCentral

22.

Elovaara I, Kuusisto H, Paalavuo R, Särkijärvi S, Lehtimäki T, Huhtala H, Vilpo J: Effect of high-dose methylprednisolone treatment on CCR5 expression on blood cells in MS exacerbation. Acta Neurol Scand. 2006, 113: 163-6. 10.1111/j.1600-0404.2005.00566.x.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/10/113/prepub

Title: Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica
Authors: Akiyuki Uzawa
Masahiro Mori
Sei Hayakawa
Saeko Masuda
Fumio Nomura
Satoshi Kuwabara
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2010
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/1471-2377-10-113

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2010

Does suprascapular nerve block reduce shoulder pain following stroke: a double-blind randomised controlled trial with masked outcome assessment

Growth in Children with Cerebral Palsy during five years after Selective Dorsal Rhizotomy: a practice-based study

Microemboli-monitoring during the acute phase of ischemic stroke: Is it worth the time?

Microvessel changes after post-ischemic benign and malignant hyperemia: experimental study in rats

Conduction in ulnar nerve bundles that innervate the proximal and distal muscles: a clinical trial

Frequency and clinical patterns of stroke in Iran - Systematic and critical review