TY - JOUR
T1 - MHC-restriction, cytokine profile, and immunoregulatory effects of human T cells specific for TCR Vβ CDR2 peptides
T2 - Comparison with myelin basic protein-specific T cells
AU - Chou, Y. K.
AU - Weinberg, A. D.
AU - Buenafe, A.
AU - Bourdette, D. N.
AU - Whitham, R.
AU - Kaleeba, J. A.R.
AU - Robey, I. F.
AU - Kavanagh, D. G.
AU - Offner, H.
AU - Vandenbark, A. A.
PY - 1996/9/15
Y1 - 1996/9/15
N2 - HLA-DR2+ patients with multiple sclerosis (MS) that respond to vaccination with TCR Vβ5.2-38-58 peptides have increased frequencies of TCR peptide-specific T cells, reduced frequencies of myelin basic protein (MBP)- specific T cells, and a better clinical course than non-responders. To evaluate possible network regulation of MBP responses by TCR peptide-specific T cells, we compared properties of both cell types. Both MBP- and TCR peptide-specific T cell clones were CD4+ and predominantly HLA-DR restricted. HLA-DR2, which is in linkage disequilibrium in MS patients, preferentially restricted TCR peptide-specific clones as well as MBP-specific responses in HLA-DR2 and DR2,3+ donors. Within the DR2 haplotype, however, both DRβ1*1501 and DRβ5*0101 alleles could restrict T cell responses to Vβ CDR2 peptides, whereas responses to MBP were restricted only by DRβ5*0101. TCR peptide-specific clones expressed message for Th2 cytokines, including IL-4, IL-5, IL-6, IL-10, and TGF-β, whereas MBP-specific T cell clones expressed the Th1 cytokines IFN-γ and IL-2. Consistent with the Th2- like cytokine profile, TCR peptide-specific T cell clones expressed higher levels of CD30 than MBP-specific T cells. Culture supernatants from TCR peptide-specific T cell clones, but not from MBP- or Herpes simplex virus- specific T cells, inhibited both proliferation responses and cytokine message production of MBP-specific T cells. These results demonstrate distinct properties of MBP and TCR peptide-specific T cells, and indicate that both target and bystander Th1 cells can be inhibited by Th2 cytokines secreted by activated TCR peptide-specific T cells. These data support the rationale for TCR peptide vaccination to regulate pathogenic responses mediated by oligoclonal T cells in human autoimmune diseases.
AB - HLA-DR2+ patients with multiple sclerosis (MS) that respond to vaccination with TCR Vβ5.2-38-58 peptides have increased frequencies of TCR peptide-specific T cells, reduced frequencies of myelin basic protein (MBP)- specific T cells, and a better clinical course than non-responders. To evaluate possible network regulation of MBP responses by TCR peptide-specific T cells, we compared properties of both cell types. Both MBP- and TCR peptide-specific T cell clones were CD4+ and predominantly HLA-DR restricted. HLA-DR2, which is in linkage disequilibrium in MS patients, preferentially restricted TCR peptide-specific clones as well as MBP-specific responses in HLA-DR2 and DR2,3+ donors. Within the DR2 haplotype, however, both DRβ1*1501 and DRβ5*0101 alleles could restrict T cell responses to Vβ CDR2 peptides, whereas responses to MBP were restricted only by DRβ5*0101. TCR peptide-specific clones expressed message for Th2 cytokines, including IL-4, IL-5, IL-6, IL-10, and TGF-β, whereas MBP-specific T cell clones expressed the Th1 cytokines IFN-γ and IL-2. Consistent with the Th2- like cytokine profile, TCR peptide-specific T cell clones expressed higher levels of CD30 than MBP-specific T cells. Culture supernatants from TCR peptide-specific T cell clones, but not from MBP- or Herpes simplex virus- specific T cells, inhibited both proliferation responses and cytokine message production of MBP-specific T cells. These results demonstrate distinct properties of MBP and TCR peptide-specific T cells, and indicate that both target and bystander Th1 cells can be inhibited by Th2 cytokines secreted by activated TCR peptide-specific T cells. These data support the rationale for TCR peptide vaccination to regulate pathogenic responses mediated by oligoclonal T cells in human autoimmune diseases.
KW - T cell receptor Vβ chain
KW - Th1 cells
KW - Th2 cells
KW - cytokines
KW - multiple sclerosis
KW - myelin basic protein (MBP)
KW - second complementarity-determining region (CDR2)
UR - http://www.scopus.com/inward/record.url?scp=10144236520&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10144236520&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-4547(19960915)45:6<838::AID-JNR21>3.0.CO;2-Q
DO - 10.1002/(SICI)1097-4547(19960915)45:6<838::AID-JNR21>3.0.CO;2-Q
M3 - Article
C2 - 8892096
AN - SCOPUS:10144236520
SN - 0360-4012
VL - 45
SP - 838
EP - 851
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 6
ER -