The syngeneic mixed leukocyte reaction: an autoreactive self-renewing cellular network for mature T lymphocytes.
The functional properties of responding T lymphocytes and the nature of the antigenic stimulus in the guinea pig Syngeneic Mixed Leukocyte Reaction (SMLR) are reviewed. The evidence presented here indicates that the SMLR is a polyclonal T cell proliferative response of several distinct antigen-specific clones by virtue of their reactivity with self Ia (I-region-encoded antigens) molecules expressed by accessory cells. Clonal analysis of SMLR-responding cells indicates that individual T cell colonies proliferate in response to syngeneic, unmodified macrophages, but not in response to I-region-disparate macrophages. This autoreactive response of T cell colonies cannot be ascribed to exposure to any extrinsic antigen, and is completely blocked by monoclonal anti-Ia antibodies. Each individual SMLR-T cell colony recognizes a particular Ia epitope on the autologous stimulating cell. Clonal analysis of extrinsic antigen-specific responses revealed three types of proliferating T cell colonies: antigen-specific, Ia-restricted; autoreactive, Ia-restricted; and antigen-specific/autoreactive, Ia-restricted. The finding of T cell colonies with antigen specificity but that could also be stimulated by Ia alone lends support to the hypothesis that the SMLR is a polyclonal T cell response to self Ia molecules. The possible in vivo attributes of the SMLR, and its main effector and regulatory mechanisms are discussed in terms of these findings.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D000939:Epitopes; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II