Regulation of T cell immunity and tolerance in vivo by CD4

Xiaoli Shen, Rolf König

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Previous experiments showed that peptides corresponding to a major CD4-binding site on the β2 domain of MHC class II molecules, IAβ134-148, enhance responses by CD4+ T lymphocytes to antigen, allo-antigen and bacterial superantigen in vitro, and to soluble protein in vivo. To determine whether peptide IAβ134-148 acted by inhibiting antigen-induced T cell tolerance, ovalbumin-specific CD4+ lymph node (LN) T cells from TCR transgenic DO.11.10 mice were adoptively transferred into H-2 syngeneic BALB/c recipients. Tolerance was then induced by injecting antigen i.v. When peptide IAβ134-148 was used to interfere with CD4-MHC class II interactions, accumulation of clonotype-positive T lymphocytes in the LN and induction of T cell tolerance in vivo were delayed. The mechanism by which peptide IAβ134-148 inhibited T cell tolerance included the peptide's ability to block activation-induced cell death. Further, antigen-specific splenic T lymphocytes were not tolerized in IAβ134-148-treated mice, providing a reservoir of T cells that could respond to a secondary immunization. The results reported here suggest that participation of the T cell co-receptor, CD4, in TCR signaling differentially affected both T cell migration and the induction of antigen-specific tolerance. Therefore, in this in vivo model system, the combined strength of all signals received (e.g. via TCR, co-receptors and co-stimulators) determined whether T cell immunity or apoptosis and tolerance resulted from antigenic stimulation. These findings are potentially important for the development of reagents to enhance vaccine efficacy and tumor immunity.

Original languageEnglish (US)
Pages (from-to)247-257
Number of pages11
JournalInternational immunology
Volume10
Issue number3
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Regulation of T cell immunity and tolerance in vivo by CD4'. Together they form a unique fingerprint.

Cite this