PULSE CYCLOPHOSPHAMIDE PLUS METHYLPREDNISOLONE INDUCES MYELIN-ANTIGEN-SPECIFIC IL-4-SECRETING T-CELLS IN MULTIPLE-SCLEROSIS PATIENTS

Multiple sclerosis (MS) is a presumed. cell-mediated Th1-type autoimmu ne disease. Thus therapies which decrease T cells secreting IFN-gamma production or increase IL-4 production would be expected to have an am eliorating effect on MS. We have previously reported increased anti-CD 3-induced IL-4 secretion by T cells in progressive MS patients treated with cyclophosphamide plus methylprednisolone (CY/MP) which was assoc iated with eosinophilia. To investigate whether the increased IL-4 sec retion was myelin antigen specific, we generated 3990 short-term T cel l lines to myelin basic protein (MBP), proteolipid protein (PLP), or t etanus toxoid (TT) from 31 progressive MS patients: 11 MS patients tre ated with CY/MP, 10 MS patients treated with MP alone, and 10 untreate d MS patients. We found increased frequencies of both MBP- and PLP-spe cific IL-4-secreting T cell lines in CY/MP-treated patients compared t o untreated MS patients. However, no change in the frequency of TT-spe cific IL-4-secreting T cells was observed. MP treatment alone did not increase the frequency of antigen-specific IL-4-secreting T cell Lines . These results demonstrate immune deviation favoring Th2-type respons es specific to autoantigens following pulse cyclophosphamide therapy i n MS patients, (C) 1998 Academic Press.