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Related Experiment Videos

Alloreactive cytotoxic T cells can develop and function in mice lacking both CD4 and CD8

M W Schilham1, W P Fung-Leung, A Rahemtulla

  • 1Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto.

European Journal of Immunology
|June 1, 1993
PubMed
Summary

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Mice lacking CD4 and CD8 genes surprisingly developed alpha beta T cells. These T cells can mount cytotoxic responses against alloantigens without CD8, challenging previous understanding of T cell development and function.

Area of Science:

  • Immunology
  • T cell biology
  • Transplantation immunology

Background:

  • CD4 and CD8 are critical co-receptors for T cell activation and function.
  • The role of CD8 in cytotoxic T cell responses, particularly alloreactive responses, is well-established.
  • Understanding T cell development and effector function in the absence of these co-receptors is crucial for immunology.

Purpose of the Study:

  • To investigate T cell development and function in mice lacking both CD4 and CD8 genes.
  • To determine if alloreactive cytotoxic T cells can develop and function without CD8.
  • To assess the in vivo rejection of allogeneic skin transplants in CD4-8- mice.

Main Methods:

  • Generation of CD4-8- knockout mice using homologous recombination in embryonic stem cells.

Related Experiment Videos

  • Analysis of T cell populations, including alpha beta T cell receptor expression.
  • In vitro stimulation of T cells with alloantigens and viral antigens to assess cytotoxic responses.
  • In vivo skin transplantation assays using fully allogeneic and minor antigen-mismatched grafts.

    • Main Results:

    • CD4-8- mice possess significant numbers of alpha beta T cells.
    • Alloreactive cytotoxic T cells, expressing alpha beta T cell receptor and recognizing MHC class I, were generated in CD4-8- mice.
    • These alloreactive cytotoxic T cells exhibited effector function both in vitro and in vivo, rejecting fully allogeneic skin grafts but not minor antigen grafts.
    • Virus-specific cytotoxic T lymphocytes were not detected.

    Conclusions:

    • Alloreactive cytotoxic T cells can develop, mature, and exert effector functions in vivo and in vitro independently of CD8.
    • The absence of CD8 does not preclude the development of MHC class I-restricted alloreactive cytotoxic T cells.
    • These findings suggest alternative pathways for cytotoxic T cell development and function in the absence of canonical co-receptors.