Immunoregulation through CD8 (Ly‐2): state of aggregation with the α/β/CD3 T cell receptor controls interleukin 2‐dependent T cell growth

The activation of T lymphocytes by an antigenic challenge requires that the CD3 T cell receptor α/β (TcR) is bound to an appropriate ligand, i.e. major histocompatibility complex antigen, on an antigen‐presenting cell. In addition, numerous studies suggest that the accessory molecules CD4 and CD8 participate in the recognition process, and may have inhibitory as well as augmenting effects depending on the ways in which they participate. In the present study we attempt to define the conditions by which CD8 exerts enhancing and inhibitory effects on resting CD8 T cell activation, and which parameters of activation are regulated through participation of CD8/CD4. We find that experimental procedures leading to TcR‐CD8 aggregation induce T cell activation whereas experimental procedures preventing TcR‐CD8 aggregation inhibit T cell activation. CD8/CD4‐induced variations in the extent of T cell activation are apparent as variations in interleukin 2 (IL 2)‐dependent growth and in the number of blastoid cells bearing IL 2 receptors. Inhibition of CD8 T cell activation is successful only if the majority, if not all CD8 molecules are occupied by soluble antibody. This latter finding argues against the suggestion of other groups that CD8 may be a receptor for negative signaling. Rather, the results support the alternative notion that a basal level of TcR‐CD8 aggregation, existing in the resting state or induced by TcR‐ligand interaction, is an essential prerequisite for CD8 T cell activation. Enhancement or depression of this basal level of aggregation causes facilitation or inhibition, respectively, of activation. This may be a mechanism for the regulation of IL 2‐dependent clonal expansion of T cells in immune responses.