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Related Experiment Videos

CD49d overexpression and T cell autoimmunity.

Ru-Ran Mo1, Julie K Eisenbraun, Joanne Sonstein

  • 1Divisions of Geriatric Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|July 9, 2003
PubMed
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Overexpressing alpha(4) integrin (CD49d) in T cells induces autoreactivity but not autoimmunity. This suggests T cell cytotoxicity, not proliferation, drives autoimmune responses in this model.

Area of Science:

  • Immunology
  • Cell Biology
  • Autoimmunity

Background:

  • T cell integrins mediate cell adhesion and signaling.
  • Overexpression of beta(2) integrin LFA-1 in T cells can induce autoreactivity and autoimmunity.
  • The role of other T cell integrins, like alpha(4) integrin (CD49d), in T cell autoreactivity is not well understood.

Purpose of the Study:

  • To investigate the functional consequences of CD49d overexpression in T cells.
  • To determine if CD49d overexpression induces T cell autoreactivity and autoimmunity.
  • To compare the effects of CD49d overexpression with LFA-1 overexpression.

Main Methods:

  • Transfection of murine CD49d cDNA into D10.G4.1 (D10) T cells.
  • Assessment of T cell proliferation in response to antigen-presenting cells (APCs).

Related Experiment Videos

  • Evaluation of T cell adhesion to endothelial cells in vitro.
  • Analysis of T cell homing to spleen in vivo.
  • Assay for autoreactive cytotoxicity.

    • Main Results:

    • CD49d-overexpressing D10 cells exhibited autoreactivity, proliferating in response to APCs MHC class II-dependently without nominal antigen.
    • CD49d overexpression increased T cell adhesion to endothelial cells and splenic homing in vivo.
    • Unlike LFA-1 overexpression, CD49d overexpression did not lead to autoreactive cytotoxicity or induce in vivo autoimmunity.
    • T cell autoreactivity was induced by CD49d overexpression, but autoimmunity was not.

    Conclusions:

    • CD49d overexpression is sufficient to induce T cell autoreactivity.
    • The ability to induce in vivo autoimmunity in this model is linked to T cell cytotoxicity, not T cell proliferation.
    • Findings differentiate the roles of LFA-1 and CD49d in T cell-mediated autoimmune responses.