Research Proposal: Type I interferons have been shown to lead to differential expansion of subsets of gammadelta T lymphocytes in cattle. The mechanism of this expansion has not been identified, but the direct anti-proliferative effect of type I interferons on T lymphocytes indicates that type I interferon must have additional mechanisms to stimulate expansion of CD8+ gammadelta T cells. Type I interferons induce IL-15 production by dendritic cells and have been shown to stimulate selective expansion of CD8+ aphabeta T cells in mice. The selective expansion in mice correlated with higher density of some subunits of the IL-15 receptors on the cell surface. We propose to examine the mechanism(s) of selective expansion of CD8+ gammadelta T cells in response to type I interferon. We will investigate the hypothesis that WCI CD8+ gammadelta T cells preferentially expand in culture with type I IFN as a result of higher density of surface expression of one or more subunits of the IL-15 receptor on this cell subset. The use of cattle allows easier access to high numbers of gammadelta T cells and provides a previously described system with CD8+ and CD8 populations of gammadelta T cells respond differently in culture with type I interferons. This project will allow a better understanding of gammadelta T cell biology with the long-term goal of targeting certain lymphocyte subsets in the development of immune responses. The Candidate: The candidate is a veterinarian completing a residency in comparative anatomical pathology and is a Ph.D. candidate. The candidate has completed most of his pathology residency, didactic course work, and is actively involved in the research phase of a combined residency/PhD program. This proposal constitutes his plan to complete doctoral research focusing on the immunology at Washington State University. Environment: The Department of Veterinary Microbiology and Pathology provides both modern research facilities for infectious disease research and a highly interactive training environment including intra- and interdisciplinary graduate education, residency programs, and extensive collaboration both within and outside the university. The sponsors collaborate closely in research and have successfully mentored clinicians, graduate students, and post-doctoral fellows to research independence.
|Rogers, Aric N; Vanburen, Denille G; Zou, Baixiang et al. (2006) Characterization of WC1 co-receptors on functionally distinct subpopulations of ruminant gamma delta T cells. Cell Immunol 239:151-61|
|Lahmers, Kevin K; Hedges, Jodi F; Jutila, Mark A et al. (2006) Comparative gene expression by WC1+ gammadelta and CD4+ alphabeta T lymphocytes, which respond to Anaplasma marginale, demonstrates higher expression of chemokines and other myeloid cell-associated genes by WC1+ gammadelta T cells. J Leukoc Biol 80:939-52|
|Lahmers, Kevin K; Norimine, Junzo; Abrahamsen, Mitchell S et al. (2005) The CD4+ T cell immunodominant Anaplasma marginale major surface protein 2 stimulates gammadelta T cell clones that express unique T cell receptors. J Leukoc Biol 77:199-208|