DEFECTIVE PRODUCTION OF ANTIINFLAMMATORY CYTOKINE, TGF-BETA BY T-CELLLINES OF PATIENTS WITH ACTIVE MULTIPLE-SCLEROSIS

Activated T lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). These T cells secrete both pro-and anti-infla mmatory cytokines. We have studied the production of these two kinds o f cytokines by PBL of patients with MS and compared it with normal con trols and other autoimmune diseases (OAD). PBL of 29 patients with MS, 14 patients with OAD, and 14 healthy normal controls were cultured fo r 5 wk. PBL of MS patients produced more pro-inflammatory cytokines, I L-2, IFN-gamma and TNF/lymphotoxin, and less anti-inflammatory cytokin e, TGF-beta, during wk 2 to 4 in culture than PBL of normal controls. PBL of MS patients also produced more IL-2 and TNF/lymphotoxin than PB L of OAD patients. Decreased TGF-beta production by lymphocytes of pat ients with MS correlated directly with disease activity. MS patients w ith active disease produced less TGF-beta than MS patients with stable disease. The cells producing TGF-beta were primarily CD8(+)T cells an d CD45RA(+)T cells. These findings emphasize the complexity of immune response in MS patients and suggest that the increased production of p ro-inflammatory cytokines by lymphocytes of patients with MS, combined with the decreased production of TGF-beta (anti-inflammatory cytokine ), may play an important role in the mechanisms and manifestations of MS.