INITIATION OF T CELL IMMUNE RESPONSES IN GUT MUCOSA

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We propose to examine in detail the participation and function of different lymphoid cells in gut associated lymphoid tissues (GALT) in the development of mucosal T cell-mediated responses of delayed hypersensitivity (DH) and cell-mediated lympholysis (CML) to orally administered hapten. We have chosen to study these two T cell-mediated immune responses not only because very little is known about their occurrence at the mucosal and other organized lymphoid tissues of the gut, but also because these responses may provide local protection against pathogenic enteric viruses, bacteria, and parasites. We will determine the time course of development of hapten specific DH and cytotoxic T lymphocytes (CTL) in GALT as well as changes in morphology and epithelial cell kinetics that occur in small intestine after feeding hapten to the mice. Whether the kinetics and the magnitude of these two responses can be altered will be determined by pretreating animals with cyclophosphamide or feeding the hapten more than once. The ability of purified immune T cells isolated from GALT to adoptively transfer DH, to develop hapten induced T cell proliferation, and to produce migration inhibition factor (MIF) will be examined. Whether T helper cells that assist in vivo DH induction are present in GALT of hapten-fed animals will be examined by their ability to produce hapten specific helper factor that aids development of in vivo DH response. The phenotypic markers on the surface of GALT TDH and TH(DH), hapten specificity and any genetic restriction of their function will be examined. The capacity of the GALT lymphocytes to generate CTLs and produce lymphokines (interleukin 2 and differentiation factor) that are required for the generation of CTLs in vitro will be assessed. The frequencies of precursors of hapten specific CTLs (p-CTL) and TH secreting IL2 among various lymphoid populations of GALT will be determined by limiting dilution analysis (LDA). The experimental work proposed here will allow us to acquire information about functional capabilities of GALT lymphocytes in the induction of mucosal T cell-mediated responses that may provide protection against dietary and pathogenic antigens or that may have adverse effects on the intestine.