MHC-RESTRICTION, CYTOKINE PROFILE, AND IMMUNOREGULATORY EFFECTS OF HUMAN T-CELLS SPECIFIC FOR TCR V-BETA CDR2 PEPTIDES - COMPARISON WITH MYELIN BASIC PROTEIN-SPECIFIC T-CELLS

HLA-DR2+ patients with multiple sclerosis (MS) that respond to vaccina tion with TCR V beta 5.2-38-58 peptides have increased frequencies of TCR peptide-specific T cells, reduced frequencies of myelin basic prot ein (MBP)-specific: T cells, and a better clinical course than non-res ponders. To evaluate possible network regulation of MBP responses by T CR peptide-specific T cells, we compared properties of both cell types , Both MBP- and TCR peptide-specific T cell clones were CD4(+) and pre dominantly HLA-DR restricted, HLA-DR2, which is in linkage disequilibr ium in MS patients, preferentially restricted TCR peptide-specific clo nes as well as MBP-specific responses in HLA-DR2 and DR2,3+ donors. Wi thin the DR2 haplotype, however, both DR beta1501 and DR beta 5*0101 alleles could restrict T cell responses to V beta CDR2 peptides, where as responses to MBP were restricted only by DR beta 50101. TCR peptid e-specific clones expressed message for Th2 cytokines, including IL-4, IL-5, IL-6, IL-10, and TGF-beta, whereas MBP-specific T cell clones e xpressed the Th1 cytokines IFN-gamma and IL-2. Consistent with the Th2 -like cytokine profile, TCR peptide-specific T cell clones expressed h igher levels of CD30 than MBP-specific T cells. Culture supernatants f rom TCR peptide-specific T cell clones, but not from MBP- or Herpes si mplex virus-specific T cells, inhibited both proliferation responses a nd cytokine message production of MBP-specific T cells. These results demonstrate distinct properties of MBP and TCR peptide-specific T cell s, and indicate that. both target and bystander Th1 cells can be inhib ited by Th2 cytokines secreted by activated TCR peptide-specific T cel ls. These data support the rationale for TCR peptide vaccination to re gulate pathogenic responses mediated by oligoclonal T cells in human a utoimmune diseases. (C) 1996 Wiley-Liss, Inc.