March 1, 1999Transplantation
Cd2 and Cd3 Receptor-Mediated Tolerance
Authors
Discussion
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Implication
Preclinical study demonstrates allograft tolerance occurs without full T cell activation in mice, indicating that CD3-specific signaling drives immune acceptance.
Key Points
- To identify which components of T cell activation and receptor signaling pathways are required for anti-CD2 and anti-CD3epsilon antibody-mediated allograft tolerance.
- Treated murine allograft recipients with anti-CD2 alongside either FcgammaR-binding IgG or non-binding IgG3 anti-CD3epsilon monoclonal antibodies.
- Assessed tolerance induction in allograft recipients with in vivo FcgammaR blockade, FcgammaR deficiency, or interleukin-2 and interleukin-2 receptor neutralization.
- Replaced anti-CD3epsilon with an anti-TCRbeta antibody to examine differential down-modulation of TCR/CD3 complex subunits, specifically TCRbeta and TCRzeta.
- Co-administration of anti-CD2 with either FcgammaR-binding or non-binding anti-CD3epsilon induced tolerance with equal efficacy.
- Tolerance induction was unaffected by in vivo FcgammaR blockade, host FcgammaR deficiency, or antibody blockade of IL-2 or IL-2R.
- Anti-TCRbeta failed to synergize with anti-CD2 to induce tolerance, failing to induce the anti-CD2-enhanced down-modulation of TCRbeta and TCRzeta observed with anti-CD3epsilon.
Cite This Study
Punch et al. (1999) studied this question.