EFFECTORS IN THE ALLOGRAFT RESPONSE

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The aim of this grant proposal is to determine under what conditions delayed type hypersensitivity (DTH) reactions play a role in the rejection of allografts. Three criteria which define the capacity of a sensitized lymphocyte in contact with its specific alloantigen to elicit a DTH have been postulated: (1) the capacity to transfer delayed footpad swelling in a syngeneic host, (2) the capacity to recruit circulating radio-labelled lymphocytes, increase regional blood flow and alter vascular permeability, and (3) the capacity to induce naive macrophages to alter function or injure tissue in vitro. Assays for each of these components of DTH reactions have been established. Carefully characterized subpopulations of cells from sponge matrix allografts across defined histocompatibility barriers (Class 1, Class 2, combinations of Class 1 and 2, minor antigenic loci) will be assayed for their capacity to satisfy DTH criteria. Only a single recipient strain of mouse (B10.AQR) will be used so that the comparisons between cell populations can be standardized for all genetic disparities. Alloantigen sensitizied cloned T cells isolated frm sponge matrix allografts with well characterized helper or cytotoxic properties will be compared in their DTH ability with subpopulations from the graft. Particular attention will be focused on clones with helper function responding to class 2 alloantigens. We expect to be able to correlate capacity of a coned T cell population to elicit the various DTH phenomena wih its antigenic specificity, its surface marker and functional phenotype, and with its capacity to secrete lymphokines in vitro. We hope to elucidate the mechanisms of tissue destruction during graft rejection in the total absence of cytotoxic T cells such as that seen during the rejection of grafts disparate only at the class 2 loci.