Cytotoxic T lymphocyte antigen-4 (CTLA-4/CD152) is a member of the CD28 family of T cell effector antigens. Current belief, based primarily on results from gene-deleted mice, is that CTLA-4 promotes suppression of T cell proliferation. In this manuscript, Mark Slifka and colleagues compare antiviral responses of unmanipulated virus-specific CTLA-4 and CTLA-4 T cells. The results of this work su...

The CTLA-4 pathway is a key regulator of T cell activation and a critical failsafe against autoimmunity. Although early models postulated that CTLA-4 transduced a negative signal, in vivo evidence suggests that CTLA-4 functions in a cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function in vivo appears to be cell-extrinsic, has been an on...

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