Definition of T cell subsets

CD8 represents the first cell surface glycoprotein used to define T cell subsets. Studies into the cellular basis of the immune response had shown that T lymphocytes mediated a wide variety of immunological functions. These cells generated cytotoxic responses to alloantigens, exerted helper and suppressor effects on the production of antibodies by B cells and initiated both delayed-type inflammatory responses and graft-versus-host responses. These findings could be explained by one of two alternative hypotheses. A single mature T lymphocyte, after activation by antigen, could give rise to cells capable of mediating the complete range of T cell responses. Alternatively, each T cell function might be mediated by a subset of T cells programmed during differentiation to express a limited range of immunological functions.

A direct approach to this question made use of alloantibodies that defined cell surface differentiation antigens, called Ly antigens, found on mouse thymocytes and a fraction of peripheral lymphocytes. Since these alloantigens had not yet been detected on the surface of nonlymphoid cells, it was hoped that they might represent components expressed exclusively on the surface of lymphocytes undergoing thymus-dependent differentiation. Lyt-2, since renamed CD8, and Lyt-3 represent cell surface antigens encoded by two closely linked genes. Lyt-2T3 ' cells accounted for approximately half of peripheral T cells and included those cells required for generation of cytotoxic activity and excluded T cells that mediated helper activity. Additional studies of the major histocompatibility complex (MHC) specificity of CD8+ and CD8" subclasses of T cells revealed that thymus-dependent differentiation gave rise to at least two separate sublines of mature T cells. The CD8~ subset was programmed to amplify a number of immune responses and was preferentially activated by class II MHC products in association with antigenic peptides. The CD8+ subset was programmed for the development of cytotoxic T lymphocyte (CTL) activity and responded preferentially to class I MHC products in association with antigenic peptides. These studies showed that thymus-dependent differentiation resulted in two lineages of T cells, CD84" and CD8 , equipped to recognize and respond to products of the MHC that were foreign by virtue of polymorphic variation (alloantigen) or because they had been modified by association with nonself peptides. Selective engagement of either screening system by foreign or altered class I or class II MHC region products activated a series of immune reactions already programmed in one or another activated T cell subset.

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