Abstract
A comprehensive peripheral blood immunophenotype analysis of 16 multiple sclerosis (MS) patients was performed by three-color flow cytometric analysis, and the results were compared with those for age-matched healthy controls. The cell subsets quantified included T cells (CD3+), B cells (CD19+), NK cells (CD56+), CD4+ and CD8+ T cells, cytotoxic (CD28+) and suppressor precursor (CD28-) CD8+ T cells, CD45RA+ and CD45RO+ T cells (CD4+ and CD8+), and CD5+ T and B cells. Analysis of MS patients' peripheral blood revealed essentially normal levels of total T, B, and NK cells. In agreement with results obtained by other investigators, it was found that MS patients had an increased CD4/CD8 ratio, primarily due to a decrease in CD8+ T cells. MS patients were found to have a significantly decreased level of suppressor precursor (CD28-) CD8+ T cells compared with that of controls but to have normal levels of cytotoxic (CD28+) CD8+ T cells. These data indicate that MS patients do not have a general decrease in CD8+ T cells but that they have a specific decrease in the suppressor precursor subset only and normal levels of cytotoxic CD8+ T cells. MS patients also had a significant increase in memory (CD45RO+) CD4+ T cells and displayed a trend towards a decrease in naive (CD45RA+) T cells in the peripheral blood.
Full Text
The Full Text of this article is available as a PDF (180.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chofflon M., Weiner H. L., Morimoto C., Hafler D. A. Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4+ 2H4+) T cells in multiple sclerosis. Ann Neurol. 1988 Aug;24(2):185–191. doi: 10.1002/ana.410240203. [DOI] [PubMed] [Google Scholar]
- Clements J. L., Winslow G., Donahue C., Cooper S. M., Allison J. P., Budd R. C. Co-stimulation via CD28 induces activation of a refractory subset of MRL-lpr/lpr T lymphocytes. Int Immunol. 1993 Nov;5(11):1451–1460. doi: 10.1093/intimm/5.11.1451. [DOI] [PubMed] [Google Scholar]
- Freedman M. S., Ruijs T. C., Blain M., Antel J. P. Phenotypic and functional characteristics of activated CD8+ cells: a CD11b-CD28- subset mediates noncytolytic functional suppression. Clin Immunol Immunopathol. 1991 Aug;60(2):254–267. doi: 10.1016/0090-1229(91)90068-l. [DOI] [PubMed] [Google Scholar]
- Friccius H., Siegels-Hübenthal P., Rehbein A., Schlotz E., Pawelec G. Induction of hyporesponsiveness in human lymphocytes-T despite their expression of both the co-receptor CD28 and its ligand B7. Cell Immunol. 1993 Oct 15;151(2):283–290. doi: 10.1006/cimm.1993.1238. [DOI] [PubMed] [Google Scholar]
- Gambi D., Porrini A. M., Giampietro A., Macor S. CD21+ (B2 antigen+) cell decrement and CD4+CD29+ (helper-inducer) cell increment suggest an activation of cell immune reactivity in multiple sclerosis. J Neuroimmunol. 1991 Aug;33(2):97–102. doi: 10.1016/0165-5728(91)90053-a. [DOI] [PubMed] [Google Scholar]
- Gould K. E., Swanborg R. H. T and B cell responses to myelin basic protein and encephalitogenic epitopes. J Neuroimmunol. 1993 Jul;46(1-2):193–198. doi: 10.1016/0165-5728(93)90249-x. [DOI] [PubMed] [Google Scholar]
- Hafler D. A., Weiner H. L. MS: a CNS and systemic autoimmune disease. Immunol Today. 1989 Mar;10(3):104–107. doi: 10.1016/0167-5699(89)90236-3. [DOI] [PubMed] [Google Scholar]
- Hauser S. L., Bhan A. K., Gilles F., Kemp M., Kerr C., Weiner H. L. Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions. Ann Neurol. 1986 Jun;19(6):578–587. doi: 10.1002/ana.410190610. [DOI] [PubMed] [Google Scholar]
- Kastrukoff L. F., Oger J. J., Tourtellotte W. W., Sacks S. L., Berkowitz J., Paty D. W. Systemic lymphoblastoid interferon therapy in chronic progressive multiple sclerosis. II. Immunologic evaluation. Neurology. 1991 Dec;41(12):1936–1941. doi: 10.1212/wnl.41.12.1936. [DOI] [PubMed] [Google Scholar]
- Koide J., Engleman E. G. Differences in surface phenotype and mechanism of action between alloantigen-specific CD8+ cytotoxic and suppressor T cell clones. J Immunol. 1990 Jan 1;144(1):32–40. [PubMed] [Google Scholar]
- Kurtzke J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444–1452. doi: 10.1212/wnl.33.11.1444. [DOI] [PubMed] [Google Scholar]
- Kölmel H. W., Sudau C. Cell count and ratio of helper/inducer to suppressor/cytotoxic T-cells in the cerebrospinal fluid of patients with multiple sclerosis. J Neurol. 1989 Oct;236(7):424–426. doi: 10.1007/BF00314904. [DOI] [PubMed] [Google Scholar]
- Li S. G., Ottenhoff T. H., Van den Elsen P., Koning F., Zhang L., Mak T., De Vries R. R. Human suppressor T cell clones lack CD28. Eur J Immunol. 1990 Jun;20(6):1281–1288. doi: 10.1002/eji.1830200613. [DOI] [PubMed] [Google Scholar]
- Mondino A., Jenkins M. K. Surface proteins involved in T cell costimulation. J Leukoc Biol. 1994 Jun;55(6):805–815. doi: 10.1002/jlb.55.6.805. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Hafler D. A., Weiner H. L., Letvin N. L., Hagan M., Daley J., Schlossman S. F. Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. Analysis with anti-2H4 monoclonal antibody. N Engl J Med. 1987 Jan 8;316(2):67–72. doi: 10.1056/NEJM198701083160202. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Steinberg A. D., Letvin N. L., Hagan M., Takeuchi T., Daley J., Levine H., Schlossman S. F. A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody. J Clin Invest. 1987 Mar;79(3):762–768. doi: 10.1172/JCI112882. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porrini A. M., Gambi D., Malatesta G. Memory and naive CD4+ lymphocytes in multiple sclerosis. J Neurol. 1992 Oct;239(8):437–440. doi: 10.1007/BF00856808. [DOI] [PubMed] [Google Scholar]
- Poser C. M., Paty D. W., Scheinberg L., McDonald W. I., Davis F. A., Ebers G. C., Johnson K. P., Sibley W. A., Silberberg D. H., Tourtellotte W. W. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983 Mar;13(3):227–231. doi: 10.1002/ana.410130302. [DOI] [PubMed] [Google Scholar]
- Reinherz E. L., Weiner H. L., Hauser S. L., Cohen J. A., Distaso J. A., Schlossman S. F. Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies. N Engl J Med. 1980 Jul 17;303(3):125–129. doi: 10.1056/NEJM198007173030303. [DOI] [PubMed] [Google Scholar]
- Rodeck U., Kuwert E., Scharafinski H. W., Lehmann H. J. T lymphocyte populations in multiple sclerosis. Eur Arch Psychiatry Neurol Sci. 1985;235(2):119–121. doi: 10.1007/BF00633483. [DOI] [PubMed] [Google Scholar]
- Rohowsky-Kochan C., Eiman D., Troiano R., Bansil S., Oleske J., Denny T., Cook S. D. Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases. J Neuroimmunol. 1990 Jul;28(2):161–166. doi: 10.1016/0165-5728(90)90030-q. [DOI] [PubMed] [Google Scholar]
- Rose L. M., Ginsberg A. H., Rothstein T. L., Ledbetter J. A., Clark E. A. Fluctuations of CD4+ T-cell subsets in remitting-relapsing multiple sclerosis. Ann Neurol. 1988 Aug;24(2):192–199. doi: 10.1002/ana.410240204. [DOI] [PubMed] [Google Scholar]
- SCHUMACHER G. A., BEEBE G., KIBLER R. F., KURLAND L. T., KURTZKE J. F., MCDOWELL F., NAGLER B., SIBLEY W. A., TOURTELLOTTE W. W., WILLMON T. L. PROBLEMS OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS: REPORT BY THE PANEL ON THE EVALUATION OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS. Ann N Y Acad Sci. 1965 Mar 31;122:552–568. doi: 10.1111/j.1749-6632.1965.tb20235.x. [DOI] [PubMed] [Google Scholar]
- Salvetti M., Ristori G., D'Amato M., Buttinelli C., Falcone M., Fieschi C., Wekerle H., Pozzilli C. Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis. Eur J Immunol. 1993 Jun;23(6):1232–1239. doi: 10.1002/eji.1830230606. [DOI] [PubMed] [Google Scholar]
- Silverman E. D., Somma C., Khan M. M., Melmon K. L., Engleman E. G. Abnormal T suppressor cell function in juvenile rheumatoid arthritis. Arthritis Rheum. 1990 Feb;33(2):205–211. doi: 10.1002/art.1780330208. [DOI] [PubMed] [Google Scholar]
- Trotter J. L., Clifford D. B., McInnis J. E., Griffeth R. C., Bruns K. A., Perlmutter M. S., Anderson C. B., Collins K. G., Banks G., Hicks B. C. Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis. Ann Neurol. 1989 Feb;25(2):172–178. doi: 10.1002/ana.410250211. [DOI] [PubMed] [Google Scholar]
- Zaffaroni M., Rossini S., Ghezzi A., Parma R., Cazzullo C. L. Decrease of CD4+CD45+ T-cells in chronic-progressive multiple sclerosis. J Neurol. 1990 Feb;237(1):1–4. doi: 10.1007/BF00319659. [DOI] [PubMed] [Google Scholar]
- Zaffaroni M., Rossini S., Palma R., Ghezzi A., Marforio S., Cazzullo C. L. Loss of suppressor-inducer T-cells in chronic-progressive multiple sclerosis: preliminary results. Adv Exp Med Biol. 1989;257:293–295. doi: 10.1007/978-1-4684-5712-4_32. [DOI] [PubMed] [Google Scholar]