Changes in activated T cells in the blood correlate with disease activity in multiple sclerosis.

OBJECTIVE To determine whether changes in activation markers on peripheral blood T cells correlate with disease activity in patients with multiple sclerosis. DESIGN In a prospective longitudinal study during 1 year, we analyzed the change in percentage of activated T lymphocytes in the peripheral blood of 40 patients with multiple sclerosis in relation to clinical findings and changes on brain magnetic resonance imaging (MRI) scans. The patients underwent repeated imaging of the brain (mean number of MRIs for each patient, 22) at the time blood samples were obtained as well as at monthly neurological examinations, and at the time of scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and ambulation index scale. RESULTS A change in the percentage of cells expressing the activation markers interleukin 2 receptor (CD25), class II major histocompatibility complex (MHC) (I3) or surface dipeptidyl peptidase (CD26) correlated significantly with a change in lesion volume or a change in number of gadolinium-enhancing lesions as detected on MRI. Changes in CD25( +) cells and in CD4(+) cells expressing class II MHC also correlated with changes in disability as measured by EDSS in patients with relapsing-remitting disease, and changes in CD4(+)CD25(+) cells correlated with the occurrence of attacks in patients with relapsing-remitting disease. These correlations are dependent on measurement of changes between time points sampled at 1- or 2-week intervals. CONCLUSION There is a linkage between peripheral T-lymphocyte activation as measured by cell surface markers and disease activity in patients with multiple sclerosis. Arch Neurol. 2000;57:1183-1189

[1]  R. Kikinis,et al.  Changes in serum levels of ICAM and TNF-R correlate with disease activity in multiple sclerosis , 1999, Neurology.

[2]  I. De Meester,et al.  CD26, let it cut or cut it down. , 1999, Immunology today.

[3]  R. Kikinis,et al.  Quantitative follow‐up of patients with multiple sclerosis using MRI: Technical aspects , 1999, Journal of magnetic resonance imaging : JMRI.

[4]  R. Killiany,et al.  Quantitative follow‐up of patients with multiple sclerosis using MRI: Reproducibility , 1999, Journal of magnetic resonance imaging : JMRI.

[5]  M Filippi,et al.  Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI , 1999, Neurology.

[6]  D. E. Anderson,et al.  Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis , 1998, Journal of Neuroimmunology.

[7]  H. Weiner,et al.  Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy. , 1998, The Journal of clinical investigation.

[8]  Ethan M. Shevach,et al.  CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production , 1998, The Journal of experimental medicine.

[9]  E. Shevach,et al.  CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. , 1998, Journal of immunology.

[10]  H. Weiner,et al.  Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Reingold,et al.  Defining the clinical course of multiple sclerosis , 1996, Neurology.

[12]  M. Hegen,et al.  Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response. , 1996, Journal of immunology.

[13]  H. Weiner,et al.  Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis. , 1995, The Journal of clinical investigation.

[14]  H. Weiner,et al.  Immunologic Mechanisms and Therapy in Multiple Sclerosis , 1995, Immunological reviews.

[15]  R. Gerli,et al.  Expression and functional role of 1F7 (CD26) antigen on peripheral blood and synovial fluid T cells in rheumatoid arthritis patients , 1994, Clinical and experimental immunology.

[16]  B. Fleischer,et al.  CD26: a surface protease involved in T-cell activation. , 1994, Immunology today.

[17]  G. Hansson,et al.  Adhesion molecule expression on cerebrospinal fluid T lymphocytes: Evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls , 1993, Annals of neurology.

[18]  R. Kikinis,et al.  Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging , 1992, Journal of magnetic resonance imaging : JMRI.

[19]  Ron Kikinis,et al.  4D Connected component labelling applied to quantitative analysis of MS lesion temporal development , 1992, 1992 14th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[20]  S. Nagataki,et al.  Remarkable increase in CD26-positive T cells in patients with human T lymphotropic virus type I (HTLV-I) associated myelopathy. , 1992, Internal medicine.

[21]  C. Morimoto,et al.  Biochemical characterization of CD26 (dipeptidyl peptidase IV): functional comparison of distinct epitopes recognized by various anti-CD26 monoclonal antibodies. , 1992, Molecular immunology.

[22]  D. McFarlin,et al.  Immunological aspects of demyelinating diseases. , 1992, Annual review of immunology.

[23]  M. Sharief,et al.  Association between Tumor Necrosis Factor-α and Disease Progression in Patients with Multiple Sclerosis , 1991 .

[24]  H. Weiner,et al.  Interleukin-1 corrects the defective autologous mixed lymphocyte response in multiple sclerosis. , 1991, Clinical immunology and immunopathology.

[25]  C. Baxevanis,et al.  Decreased HLA-DR antigen expression on monocytes causes impaired suppressor cell activity in multiple sclerosis. , 1990, Journal of immunology.

[26]  H. Weiner,et al.  Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid , 1989, Annals of neurology.

[27]  F. Mattioli,et al.  Absence of a correlation between T lymphocyte subsets and clinical activity in relapsing-remitting multiple sclerosis , 1989, Journal of Neuroimmunology.

[28]  H. Weiner,et al.  MS: a CNS and systemic autoimmune disease. , 1989, Immunology today.

[29]  Monica S. Perlmutter,et al.  Correlation of immunological studies and disease progression in chronic progressive multiple sclerosis , 1989, Annals of neurology.

[30]  D. Paty,et al.  Multiple sclerosis , 1988, Neurology.

[31]  H. Weiner,et al.  Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis , 1988, Annals of neurology.

[32]  Kendall A. Smith,et al.  The interleukin 2 receptor. Functional consequences of its bimolecular structure , 1987, The Journal of experimental medicine.

[33]  H. Weiner,et al.  Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. Analysis with anti-2H4 monoclonal antibody. , 1987, The New England journal of medicine.

[34]  A. Teelken,et al.  T-lymphocyte subpopulations in peripheral blood of patients with multiple sclerosis, patients with other neurological diseases and healthy controls , 1986, Clinical Neurology and Neurosurgery.

[35]  J. Antel,et al.  Defective suppressor cell function mediated by T8+ cell lines from patients with progressive multiple sclerosis. , 1986, Journal of immunology.

[36]  D. Compston,et al.  Suppressor T cells in family members of patients with multiple sclerosis. , 1986, Brain : a journal of neurology.

[37]  J. Merrill,et al.  Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain. , 1986, Journal of immunology.

[38]  S. Zeger,et al.  Longitudinal data analysis using generalized linear models , 1986 .

[39]  T. Waldmann,et al.  Only high-affinity receptors for interleukin 2 mediate internalization of ligand. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[40]  H. Weiner,et al.  Decreased autologous mixed lymphocyte reaction in multiple sclerosis , 1985, Journal of Neuroimmunology.

[41]  P. Kilian,et al.  Induction and upregulation by interleukin 2 of high-affinity interleukin 2 receptors on thymocytes and T cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[42]  E. Clark,et al.  Selective loss of a subset of T helper cells in active multiple sclerosis. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[43]  E. Reinherz,et al.  In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. , 1985, The New England journal of medicine.

[44]  W. Greene,et al.  Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen , 1984, The Journal of experimental medicine.

[45]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[46]  E. Reinherz,et al.  Immunoregulatory T‐cells and lymphocytotoxic antibodies in active multiple sclerosis: Weekly analysis over a six‐month period , 1983, Annals of neurology.

[47]  E. Reinherz,et al.  Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies. , 1980, The New England journal of medicine.