Disruption of T lymphocyte positive and negative selection in mice lacking the CD8 beta chain

Immunity. 1994 Jul;1(4):277-85. doi: 10.1016/1074-7613(94)90079-5.

Abstract

The CD4 and CD8 coreceptors have been shown to play significant roles in the differentiation and activation of helper and cytotoxic T lymphocytes (CTLs), respectively. Coordinate binding of coreceptor and T cell receptor (TCR) to the same major histocompatibility complex (MHC) molecule and coreceptor interaction with the tyrosine kinase p56lck are required for effective signaling. Whereas CD4 is a monomer, CD8 consists of either alpha alpha homodimers or alpha beta heterodimers. Signaling properties of CD8 have been ascribed to the alpha chain, which binds to both the MHC class I and to p56lck, respectively. To study CD8 beta specifically, we have generated mice defective in its expression. We observe a significant reduction in the numbers of CD8+ T cells, but these cells have normal CTL activity. By breeding CD8 beta null mice with animals expressing a class I-specific TCR transgene, we show that CD8 beta plays a significant role in both positive and negative selection of developing thymocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens / genetics*
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • DNA Primers / genetics
  • Genes, MHC Class I
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • CD8 Antigens
  • DNA Primers
  • Receptors, Antigen, T-Cell