Low and High CD8 Positive T cells in Multiple Sclerosis Patients
-
Maryam Izad
,
Mohammad Hossein Harirchian
,
Hamed Amiri
,
Farangis Najafi
,
Zahra Ghaflati
,
Zahra Salehi
Abstract
Cumulating evidence points to a key role for CD8+ T cells in the pathogenesis of multiple sclerosis.CD8 expression level was believed to be present constantly on the surface of human peripheral blood T cells. However, it was shown that peripheral blood lymphocytes may be divided by the level of CD8 expression, into CD8+high and CD8+low T cells. Now it is well established that the CD8low population of CD8+ T cells demonstrates an activated effector phenotype while the CD8+high T cells have been reported to have regulatory function. In this report we used a flow cytometric assay to compare the frequency of these two subsets in multiple sclerosis patients (n=31) with healthy age- and gender-matched controls (n=18). We found that CD8+ T cells and CD8+low T cells significantly increased in secondary progressive (SP) and primary progressive multiple sclerosis (PPMS) patients in comparison to controls (p<0.0002 and p<0.004 respectively) and also RRMS (p<0.005 and p<0.017 respectively). These results demonstrated the role of CD8low T cells in progressive form of multiple sclerosis.
1. Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol Rev 2005; 204:208-31.
2. Vukusic S, Confavreux C. Natural history of multiple sclerosis: risk factors and prognostic indicators. Curr Opin Neurol 2007; 20(3):269-74.
3. Noonan CW, Williamson DM, Henry JP, Indian R, Lynch SG, Neuberger JS. The prevalence of multiple sclerosis in 3 US communities. Prev Chronic Dis 2010; 7(1):A12.
4. Elhami SR, Mohammad K, Sahraian MA, Eftekhar H. A 20-year incidence trend (1989-2008) and point prevalence (March 20, 2009) of multiple sclerosis in Tehran, Iran: a population-based study. Neuroepidemiology 2011;36(3):141-7.
5. Sospedra M, Martin R. Immunology of multiple sclerosis.Annu Rev Immunol 2005; 23:683-747.
6. Hemmer B, Nessler S, Zhou D, Kieseier B, Hartung HP.Immunopathogenesis and immunotherapy of multiple sclerosis. Nat Clin Pract Neurol 2006; 2(4):201-11.
7. Winquist RJ, Kwong A, Ramachandran R, Jain J. The complex etiology of multiple sclerosis. Biochem Pharmacol 2007; 74(9):1321-9.
8. Lincoln MR, Montpetit A, Cader MZ, Saarela J, Dyment DA, Tiislar M, et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 2005; 37(10):1108-12.
9. Compston A, Coles A. Multiple sclerosis. Lancet 2008;372(9648):1502-17.
10. Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 2010;162(1):1-11.
11. Goverman J, Perchellet A, Huseby ES. The role of CD8(+) T cells in multiple sclerosis and its animal models. Curr Drug Targets Inflamm Allergy 2005;4(2):239-45.
12. Babbe H, Roers A, Waisman A, Lassmann H, Goebels N,Hohlfeld R, et al. Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med 2000; 192(3):393-404.
13. Junker A, Ivanidze J, Malotka J, Eiglmeier I, Lassmann H, Wekerle H, et al. Multiple sclerosis: T-cell receptor expression in distinct brain regions. Brain 2007; 130(Pt11):2789-99.
14. Trautmann A, Rückert B, Schmid-Grendelmeier P, Niederer E, Bröcker EB, Blaser K, et al. Human CD8 T cells of the peripheral blood contain a low CD8 expressing cytotoxic/effector subpopulation. Immunology 2003; 108(3):305-12.
15. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996; 46(4):907-11.
16. Twork S, Wiesmeth S, Spindler M, Wirtz M, Schipper S, Pöhlau D, et al. Disability status and quality of life in multiple sclerosis: non-linearity of the Expanded Disability Status Scale (EDSS). Health Qual Life Outcomes 2010; 8:55.
17. Vukmanovic-Stejic M, Vyas B, Gorak-Stolinska P, Noble A, Kemeny DM. Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes. Blood; 2000; 95(1):231-40.
18. De Jager PL, Rossin E, Pyne S, Tamayo P, Ottoboni L, Viglietta V, et al. Cytometric profiling in multiple sclerosis uncovers patient population structure and a reduction of CD8low cells. Brain 2008; 131(Pt 7):1701-11.
19. Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, et al. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 2006; 103(15):5941-6.
20. Ratts RB, Karandikar NJ, Hussain RZ, Choy J, Northrop SC, Lovett-Racke AE, et al. Phenotypic characterization of autoreactive T cells in multiple sclerosis. J Neuroimmunol 2006; 178(1-2):100-10.
21. Keir ME, Rosenberg MG, Sandberg JK, Jordan KA, Wiznia A, Nixon DF, et al. Generation of CD3+CD8low thymocytes in the HIV type 1-infected thymus. J Immunol 2002; 169(5):2788-96.
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| Issue | Vol 12, No 3 (2013) | |
| Section | Articles | |
| Keywords | ||
| CD8 T cells CD8 low T cells CD8 high T cells Multiple sclerosis | ||
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