MHC-restriction, cytokine profile, and immunoregulatory effects of human T cells specific for TCR Vβ CDR2 peptides: Comparison with myelin basic protein-specific T cells

Y. K. Chou, A. D. Weinberg, A. Buenafe, Dennis Bourdette, Ruth Whitham, J. A R Kaleeba, I. F. Robey, D. G. Kavanagh, Halina Offner, Arthur Vandenbark

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)838-851
Number of pages14
JournalJournal of Neuroscience Research
Volume45
Issue number6
DOIs
StatePublished - Sep 15 1996

Fingerprint

Myelin Basic Protein
Cytokines
Peptide T
T-Lymphocytes
Clone Cells
HLA-DR2 Antigen
Peptides
peptide V
Multiple Sclerosis
Vaccination
Th1 Cells
Interleukin-5
Linkage Disequilibrium
HLA-DR Antigens
Simplexvirus
Interleukin-4
Interleukin-10
Haplotypes
Autoimmune Diseases
Interleukin-2

Keywords

  • cytokines
  • multiple sclerosis
  • myelin basic protein (MBP)
  • second complementarity-determining region (CDR2)
  • T cell receptor Vβ chain
  • Th1 cells
  • Th2 cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

MHC-restriction, cytokine profile, and immunoregulatory effects of human T cells specific for TCR Vβ CDR2 peptides : Comparison with myelin basic protein-specific T cells. / Chou, Y. K.; Weinberg, A. D.; Buenafe, A.; Bourdette, Dennis; Whitham, Ruth; Kaleeba, J. A R; Robey, I. F.; Kavanagh, D. G.; Offner, Halina; Vandenbark, Arthur.

In: Journal of Neuroscience Research, Vol. 45, No. 6, 15.09.1996, p. 838-851.

Research output: Contribution to journalArticle

@article{b65595dce4434cde80465b097b019d21,
title = "MHC-restriction, cytokine profile, and immunoregulatory effects of human T cells specific for TCR Vβ CDR2 peptides: Comparison with myelin basic protein-specific T cells",
abstract = "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.",
keywords = "cytokines, multiple sclerosis, myelin basic protein (MBP), second complementarity-determining region (CDR2), T cell receptor Vβ chain, Th1 cells, Th2 cells",
author = "Chou, {Y. K.} and Weinberg, {A. D.} and A. Buenafe and Dennis Bourdette and Ruth Whitham and Kaleeba, {J. A R} and Robey, {I. F.} and Kavanagh, {D. G.} and Halina Offner and Arthur Vandenbark",
year = "1996",
month = "9",
day = "15",
doi = "10.1002/(SICI)1097-4547(19960915)45:6<838::AID-JNR21>3.0.CO;2-Q",
language = "English (US)",
volume = "45",
pages = "838--851",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "6",

}

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, Dennis

AU - Whitham, Ruth

AU - Kaleeba, J. A R

AU - Robey, I. F.

AU - Kavanagh, D. G.

AU - Offner, Halina

AU - Vandenbark, Arthur

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 - cytokines

KW - multiple sclerosis

KW - myelin basic protein (MBP)

KW - second complementarity-determining region (CDR2)

KW - T cell receptor Vβ chain

KW - Th1 cells

KW - Th2 cells

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

VL - 45

SP - 838

EP - 851

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 6

ER -