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

The objective of this study was to determine whether autoreactive T cells i n patients with multiple sclerosis (MS) are polarized and committed in thei r differentiation to a stable cytokine phenotype or whether the cytokine se cretion can be altered. We examined the cytokines secreted by myelin basic protein (MBP) as compared to tetanus toroid-reactive (TT)T cells in 12 pati ents with relapsing remitting MS (RR-MS), 9 patients with chronic progressi ve 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 pr omoting Th1 (IL-12/alpha-IL-4 mAb) or Th2 (IL-4/alpha-IL-12 mAb) cytokine s ecretion. Antigen-specific cytokine secretion from normals and MS patients could be shifted to a Th1 or Th2 type phenotype depending upon culture cond itions, indicating that the phenotype of MBP reactive T cells can be altere d even in longstanding chronic progressive MS. There were no significant di fferences in the cytokine patterns secreted by MBP reactive T cells in pati ents with MS as compared to normal individuals. However, CP-MS patients ten ded to have fewer MBP reactive T cells secreting IL-4 when cultured with IL -12/anti-IL-4 mAb and more IFN-gamma secreting MBP reactive T cells when cu ltured 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 th at fewer undifferentiated MBP-reactive cells are present in these individua ls. The most striking observation was that in contrast to the RR-MS patient s and normal controls, almost none of the MBP reactive T cells secreting cy tokines in CP-MS incorporated (3)[H]thymidine. This may be due to chronic i n vivo stimulation in the presence of IL-12, or because these T cells may h ave entered a terminally differentiated state. Nonetheless, the ability to alter the cytokine secretion of autoreactive T cell lines even in longstand ing autoimmune disease indicates that cytokine therapy might have therapeut ic benefits by switching the function of myelin reactive T cells such that they are non-pathogenic. (C) 1998 Elsevier Science B.V. All rights reserved .