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 autoimmune disease. Thus therapies which decrease T cells secreting IFN-gamma production or increase IL-4 production would be expected to have an ameliorating effect on MS. We have previously reported increased anti-CD3-induced IL-4 secretion by T cells in progressive MS patients treated with cyclophosphamide plus methylprednisolone (CY/MP) which was associated with eosinophilia. To investigate whether the increased IL-4 secretion was myelin antigen specific, we generated 3990 short-term T cell lines to myelin basic protein (MBP), proteolipid protein (PLP), or tetanus toxoid (TT) from 31 progressive MS patients: 11 MS patients treated with CY/MP, 10 MS patients treated with MP alone, and 10 untreated MS patients. We found increased frequencies of both MBP- and PLP-specific IL-4-secreting T cell lines in CY/MP-treated patients compared to untreated MS patients. However, no change in the frequency of TT-specific 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 responses specific to autoantigens following pulse cyclophosphamide therapy in MS patients.
Takashima
H
H
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
Smith
D R
DR
Fukaura
H
H
Khoury
S J
SJ
Hafler
D A
DA
Weiner
H L
HL
D000328:Adult; D001324:Autoantigens; D002460:Cell Line; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*
D001324:Autoantigens; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D013745:Tetanus Toxoid; D015847:Interleukin-4; D003520:Cyclophosphamide; D008775:Methylprednisolone