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Related Experiment Videos

Autoimmunity-prone BB rats lack functional cytotoxic T cells.

G J Prud'homme1, P H Lapchak, N A Parfrey

  • 1Department of Pathology, McGill University, Montreal, Canada.

Cellular Immunology
|June 1, 1988
PubMed
Summary

Autoimmune diabetes in BB rats develops without functional cytotoxic T cells. These rats have reduced T suppressor/cytotoxic cells that lack cytotoxic activity, even with immune-boosting cytokines.

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Area of Science:

  • Immunology
  • Endocrinology
  • Autoimmunity

Background:

  • BB rats spontaneously develop autoimmune insulin-dependent diabetes mellitus (IDDM) and thyroiditis.
  • Autoimmunity development in BB rats is thymus-dependent.
  • Previous research indicates BB rats have a deficiency in T cells, specifically those bearing the RT6 antigen and suppressor/cytotoxic T cells.

Purpose of the Study:

  • To investigate the functional capacity of T suppressor/cytotoxic (Ts/c) cells in BB rats.
  • To determine if BB rat T cells possess cytotoxic activity against target cells, including islet cells.
  • To understand the role of cytotoxic T lymphocytes in the pathogenesis of autoimmune diabetes in BB rats.

Main Methods:

  • Quantified phenotypic T suppressor/cytotoxic (Ts/c) cells (OX19+, OX8+) in lymphoid organs of BB rats.

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  • Assessed cytotoxic activity of BB rat T cells using cell-mediated lympholysis and lectin-dependent cytotoxicity assays.
  • Evaluated the effect of lymphokines (IL-2, IFN-γ) on inducing cytotoxic T lymphocytes in BB rat T cell cultures.
  • Tested the ability of activated T cells from diabetic BB rats to kill major-histocompatibility-complex-matched islet cells.

    • Main Results:

    • BB rats exhibit decreased numbers of phenotypic Ts/c cells (OX19+, OX8+).
    • The Ts/c cells in BB rats lack functional cytotoxic activity against allogeneic target cells and do not generate lectin-dependent cytotoxicity.
    • Addition of cytokines (IL-2, IFN-γ) did not restore cytotoxic function in BB rat T cells.
    • Activated T cells from diabetic BB rats could not kill MHC-matched islet cells, despite their ability to transfer IDDM.

    Conclusions:

    • Autoimmune diabetes in BB rats occurs independently of functional cytotoxic T cells.
    • The pathogenesis of autoimmune diabetes in BB rats involves mechanisms other than direct T cell-mediated cytotoxicity against islet cells.
    • BB rats represent a model for studying autoimmune diseases that develop in the absence of cytotoxic T lymphocyte activity.