The degree of CD8 dependence of cytolytic T cell precursors is determined by the nature of the T cell receptor (TCR) and influences negative selection in TCR‐transgenic mice

Nathalie Auphan, John Curnow, Annick Guimezanes, Claire Langlet, Bernard Malissen, Andrew Mellor, Anne Marie Schmitt-Verhulst

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Although much has been learned about CD8 structure‐function properties, it has so far not been tested whether the nature of the TCR is sufficient to transfer the property of CD8 dependence versus non‐dependence to CD8+ cytotoxic T lymphocytes (CTL) and their precursors differentiating in T cell receptor (TCR)‐transgenic (Tg) mice. In the present study, we compared the characteristics of dependence on CD8 for stimulation of CTL precursors and antigen‐specific cytolysis by CD8+ T cells from two TCR‐Tg mice expressing respectively the TCR (Tg) from a “CD8‐dependent” and from a “CD8‐independent” CTL clone, which were both reactive against the H‐2Kb alloantigen and originated from H‐2k mice. The results indicate that the property of the Tg+CD8+ cells from H‐2k TCR‐Tg mice corresponds to that of the CTL clone of origin, demonstrating that it is linked to the nature of the TCR. Consistent with this property, Tg+CD4+ cells could also differentiate into H‐2Kb‐specific CTL when originating from the “CD8‐independent”, but not from the “CD8‐dependent” Tg‐TCR. The influence of the property of “CD8 dependence” on negative selection occurring in TCR‐Tg H‐2klb mice was apparent at two levels: (i) in the thymus, the extent of deletion was much more pronounced for the “CD8‐independent” TCR‐Tg mice; (ii) in the periphery, Tg+(hi) cells with low to negative CD8 expression were present for the “CD8‐dependent” Tg‐TCR, whereas only Tg+CD4CD8 cells with low surface Tg‐TCR and CD3 expression were found for the “CD8‐independent” Tg‐TCR, indicating that Tg+CD4CD8 cells are susceptible to tolerance induction involving TCR/CD3 surface down‐modulation. Furthermore, different in vitro conditions led to H‐2Kb‐induced stimulation of Tg+CD4CD8 cells to differentiate into CTL detected in an anti‐TCR clonotypic monoclonal antibody redirected cytolysis assay. Culture in interleukin‐2 of H‐2klb Tg+CD4CD8 cells was sufficient to induce CTL activity in the “CD8‐independent” model, whereas stimulation with cells which overexpressed H‐2Kb was required in addition to interleukin‐2 to induce CTL differentiation in the “CD8‐dependent” model. These data suggest that peripheral Tg+CD4CD8 cells present in a situation of in vivo tolerance to H‐2Kb can still be triggered by H‐2Kb with a sensitivity correlated with the degree of CD8 dependence.

Original languageEnglish (US)
Pages (from-to)1572-1577
Number of pages6
JournalEuropean Journal of Immunology
Volume24
Issue number7
DOIs
Publication statusPublished - Jan 1 1994

    Fingerprint

Keywords

  • CD8
  • Cytolytic T lymphocyte
  • T cell receptor
  • Transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this