INITIATOR T CELLS IN DELAYED-TYPE HYPERSENSITIVITY

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Delayed type hypersensitivity (DTH) reactions are in vivo examples of T cell mediated immunity. Previous work indicated that 24 hr DTH was due to antigen/MHC-Class II-restricted CD4+ (L3T4+)T cells. These DTH effector T cells have been called "inflammatory" (Th-1) T cells because they are characterized by in vitro production of I12, interferon-gamma and lymphotoxin. However, newer work from our laboratory has indicated that DTH is due to the sequential action of two different T cells. An early-acting T cell produces antigen-specific T cell factor that initiates DTH by sensitizing tissues for serotonin release. In picryl chloride (PCl) contact sensitivity, PCl-F is the prototype factor. The serotonin-mediated vasoactivity induced by PCl -F allows local recruitment of the late acting, DTH-inflammatory T cells. This proposal will focus on the T cell subpopulations that mediate DTH. We hypothesize the following: 1) that DTH-initiating T cells are functioning, primitive, relatively thymic-independent T cells; 2) that DTH- initiating T cells have a "triple-negative" surface phenotype of: Thy1+,Ly1+,Ly2-,L3T4-,CD3-or CD3-lo; and 3) that DTH-initiating T cells have antigen-only receptors that are non-MHC-restricted. If these hypotheses are correct, then systemic transferred DTH will be shown to be due to the synergistic action of CD4- DTH- initiating, and CD4+ DTH-inflammatory T cells. Thus, we plan to characterize this relatively thymic-independent T cell and its antigen-specific product. We plan to isolate and clone these cells by selecting for their unique surface phenotype and through our ability to induce this DTH-initiating T cell in vitro. We will continue to attempting to purify PCl-F and hope eventually to clone the genes that encode for this DTH-initiating factor so that it can be compared to conventional T cell receptors. Our studies, and those of others, indicate that DTH-initiating T cells are involved in contact and delayed hypersensitivity, resistance to tumors, gastrointestinal inflammation, and autoimmunity. Thus our studies on the cellular and molecular aspects of DTH initiation have broad immunological relevance.