While T lymphocytes that express the gamma delta (gamma/delta) T cell receptor represent a small subset of T cells present in lymphoid organs, gamma/delta T cells appear to predominate in epithelial tissue. This tissue localization may indicate their involvement in """"""""front line"""""""" defense mechanisms by recognition of microbial or induced antigens present at these sites. The ability to rapidly respond to pro-inflammatory cytokines may provide an important sentinel function for gamma/delta T cells. In addition to their defensive role in infectious disease, it is also becoming clear that gamma/delta T cells can play a significant regulatory role in tolerance, allergy, autoimmunity, and inflammatory disease. It has become clear that gamma/delta T cells recognize and respond to antigens and cytokines in a manner markedly different than the other major T cell, the alpha beta (alpha/beta) T cell. While a clear consensus remains to emerge, it appears that gamma/delta T cells do not generally recognize peptide epitopes in association with the MHC. Unlike alpha/beta T cells, the gamma/delta cell receptor may function more like immunoglobulin and recognize antigens directly. Another interesting feature of gamma/delta T cells is their ability to respond rapidly to cytokines produced early in the immune response. They constitutively express receptors for cytokines that are only inducible on other cell types such as alpha/beta T cells. In the proposed studies we will attempt to understand the mechanism of gamma/delta T cell function in resistance to infectious disease in a well-defined mouse mode. Mice lacking gamma/delta T cells (delta knockout mice) will be utilized in hopes of understanding cytokine production and response patterns of gamma/delta T cells during infection with Listeria monocytogenes. The regulatory role of gamma/delta T cells in the production of pro-inflammatory cytokines will be studied. An attempt will be made to determine the function, receptor specificity, and activation requirements of gamma/delta T cells.
