Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis

• Published in: Journal of neuroimmunology Vol. 91; no. 1; pp. 1 - 9
• Main Authors: Windhagen, A., E. Anderson, D., Carrizosa, A., Balashov, K., L. Weiner, H., A. Hafler, D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 02-11-1998
• Subjects: Antibodies, Monoclonal; Antibody Specificity; Autoimmunity; Cell Division - immunology; Cells, Cultured; Cytokine; Cytokines - immunology; Humans; IFN- γ; IL-4; Interferon-gamma - immunology; Interleukin-10 - immunology; Interleukin-12 - immunology; Interleukin-4 - immunology; Multiple sclerosis; Multiple Sclerosis - immunology; Myelin Basic Protein - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Autoimmunity; Multiple sclerosis; PLP=proteolipid protein; Cytokine; IL-4; IFN=interferon; TGF=transgenic growth factor; RR-MS=relapsing remitting multiple sclerosis; MBP=Myelin basic protein; CNS=central nervous system; IL=interleukin; TT=tetanus toxoid; TCR=T cell receptor; CP-MS=chronic progressive multiple sclerosis; IFN- γ
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(98)00086-1

The objective of this study was to determine whether autoreactive T cells in patients with multiple sclerosis (MS) are polarized and committed in their differentiation to a stable cytokine phenotype or whether the cytokine secretion can be altered. We examined the cytokines secreted by myelin basic protein (MBP) as compared to tetanus toxoid-reactive (TT) T cells in 12 patients with relapsing remitting MS (RR-MS), 9 patients with chronic progressive MS (CP-MS), and 14 normal individuals. A total of 5094 short term T cell lines to MBP and TT were generated in the presence of growth conditions promoting Th1 (IL-12/
α–IL-4 mAb) or Th2 (IL-4/
α–IL-12 mAb) cytokine secretion. Antigen-specific cytokine secretion from normals and MS patients could be shifted to a Th1 or Th2 type phenotype depending upon culture conditions, indicating that the phenotype of MBP reactive T cells can be altered even in longstanding chronic progressive MS. There were no significant differences in the cytokine patterns secreted by MBP reactive T cells in patients with MS as compared to normal individuals. However, CP-MS patients tended to have fewer MBP reactive T cells secreting IL-4 when cultured with IL-12/anti-IL-4 mAb and more IFN-
γ secreting MBP reactive T cells when cultured with IL-4/anti-IL-12 mAb as compared to both normal controls and RR-MS, suggesting that cells from these patients might be more polarized or that fewer undifferentiated MBP-reactive cells are present in these individuals. The most striking observation was that in contrast to the RR-MS patients and normal controls, almost none of the MBP reactive T cells secreting cytokines in CP-MS incorporated
3[
H]
thymidine. This may be due to chronic in vivo stimulation in the presence of IL-12, or because these T cells may have entered a terminally differentiated state. Nonetheless, the ability to alter the cytokine secretion of autoreactive T cell lines even in longstanding autoimmune disease indicates that cytokine therapy might have therapeutic benefits by switching the function of myelin reactive T cells such that they are non-pathogenic.