Antibody blockade of Thy‐1 (CD90) impairs mouse cytotoxic T lymphocyte induction by anti‐CD3 monoclonal antibody

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Abstract
Thy‐1 (CD90) expressed by mouse T cells is known to have signal transducing properties, but the ability of Thy‐1 to enhance cytotoxic T lymphocyte (CTL) development is not well understood. Here we show that stimulation of mouse T cells with monoclonal antibodies (mAb) to CD3, CD28 and Thy‐1 (clone G7), which were coimmobilized on polystyrene microbeads, resulted in a greater proliferative response than stimulation with only anti‐CD3 and anti‐CD28 mAb, indicating that Thy‐1 cross‐linking enhanced T cell receptor/CD28‐driven T cell activation. Consistent with this finding, Thy‐1 blockade with a soluble nonactivating anti‐Thy‐1 mAb (clone 30‐H12) inhibited anti‐CD3‐induced proliferation of CD4+ and CD8+ T cells, and the induction of cytotoxic effector cells in a dose‐dependent fashion. Interleukin‐2 synthesis and CD25 expression were also impaired by Thy‐1 blockade. The inhibitory effect involved a defect at or before the level of protein kinase C activation because the addition of phorbol ester ablated the anti‐Thy‐1‐mediated inhibition of anti‐CD3‐induced T cell activation. The CTL that were induced in the presence of blocking anti‐Thy‐1 mAb adhered to target cells but showed reduced expression of granzyme B and perforin. In contrast, Fas ligand expression and function was not affected by Thy‐1 blockade. We conclude that Thy‐1 signalling promotes the in vitro generation of CTL that kill in a granule‐dependent fashion.
Funding Information
  • Natural Sciences and Engineering Research Council of Canada