IMMUNE POTENTIAL OF ANIMAL LACKING CLASS IA MOLECULES

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This proposal investigates a unique function for CDS T cells in the immune response against infectious agents. Our major focus is on the role that CDST cells play in the innate immune response during infection with Listeria monocytogenes (LM). We recently demonstrated that antigen non specific CDS T memory cells participate in a cytokine driven innate response against LM by secreting interferon-y. Further ransfer of "innate" CDS T cells into interferon-y deficient mice protects them from infection with LM. We propose that CDST cells play a major role in the INF-y mediated innate response. In the first Aim we investigate the relative potency of CDS vs NK cells in providing this type of innate protection. We postulate that effector CDS T memory cells (TFM). which have been shown to play a minor role in the adaptive immune response play an important role in the innate response and will test thii hypothesis. In the second Aim we will examine the localization of CDS central memory cells (TOM). TEM. anc MK cells at sites of LM infection in spleen and liver. We will use mice deficient in CCR7 binding chemokine! CCL-19 and -21) to assess how this chemokine-receptor interaction affects CDS T cells in the innate response. We will also utilize new BAG transgenic mice that express Thy-1.1 as a reporter for IFN-y secretion to examine IFN-y secreting CDS and NK cells in situ. In the third Aim we will determine the role of CDS T cells in polarizing nai've CD4 T cells to the Th1 subset. In the fourth Aim we will examine by microarray analysis the gene display of CDS T cells that are activated by IL-12/18 (innate) vs those that are activated through the TcR (adaptive). In summary, this proposal will add important new information on how CDS T cells function in the innate immune response against intracellular pathogens.