Browsing by Author "Dr. Gregg Dean, Committee Member"

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Differential Thrombospondin Expression on T Lymphocytes in a Feline Immunodeficiency Virus Model
(2007-11-04) Rogers, Melinda Cadd; Dr. Sue Tonkonogy, Committee Member; Dr. Gregg Dean, Committee Member; Dr. Mary Tompkins, Committee Chair
CD4+CD25+ T regulatory cells represent an important subset of lymphocytes whose function is to suppress autoimmune disease and control normal immune responses. There is much research indicating a direct role for TGF-beta expressed on the surface of Tregs in the suppressor function of these cells. TGF-beta, whether bound to the cell surface or secreted, is produced as part of a complex that renders the cytokine inactive. Thrombospondin is the primary activator of biologically latent TGF-beta. This research demonstrates that thrombospondin is expressed on the surface of T lymphocytes isolated from the blood and lymph nodes of normal and FIV positive felines. Thrombospondin is expressed at significantly higher levels on CD4+CD25+ T lymphocytes, but can be induced in culture by activating T helper cells in the presence of LPS and IL2. We also observed that the CD4+CD25- T helper cells isolated from FIV negative control lymph nodes were able to markedly upregulate surface thrombospondin expression compared with similarly stimulated CD4+CD25- T helper cells from FIV positive sources. These findings are initial steps in working to understand the mechanism behind latent TGF-beta activation on CD4+CD25+ T regulatory cells and the role this cell type plays in FIV/HIV pathogenesis.
Feline Lentivirus enhanced CD4+CD25+ T regulatory conversion of CD4+CD25- T cells to phenotypic and functional T reg cells via the TGF-b/TGF-bR signaling pathway
(2007-08-10) Petty, Christopher Samuel; Dr. Frederick Fuller, Committee Member; Dr. Linda Martin, Committee Member; Dr. Gregg Dean, Committee Member; Dr. Wayne Tompkins, Committee Chair
The Role of the B7 Co-stimulation Pathway in Feline Immunodeficiency Virus (FIV) and Human Immunodeficiency Virus (HIV)Associated T cell depletion
(2003-03-09) Bull, Marta Eileen; Dr. Mary Tompkins, Committee Member; Dr. Wayne Tompkins, Committee Chair; Dr. Fred Fuller, Committee Member; Dr. Holly Jordan, Committee Member; Dr. Gregg Dean, Committee Member
Feline immunodeficiency virus (FIV) in the domestic cat provides a good animal model for dissecting the immunopathology associated with HIV infected individuals, as the immune dysfunction in the cat replicates the immune deterioration in humans. Lentiviruses characteristically cause a gradual loss in T-helper cells numbers and functions. A variety of mechanisms have been proposed to account for lentivirus-induced T cell depletion although none of these mechanisms alone account for all the T cell changes. The B7/cytotoxic T lymphocyte antigen four (CTLA4) signaling pathway is a major signaling pathway in the initiation and termination of T cell immune responses. The B7 receptors are normally expressed on the surface of antigen presenting cells (APC), while CD28 and CTLA4 are differentially expressed on the surface of T cells. Recent studies show that chronic stimulation in vitro or in vivo results in an unusual increase in the percent of T cells that express the B7 and CTLA4 molecules. These chronically activated T cells also up-regulate major histocompatibility complex class II molecules (MHC II) and are capable of inducing anergy and apoptosis of other activated T cells. In this study we found that individuals with a HIV or FIV infections had increased expression of B7 and CTLA4 on T cells in peripheral blood and lymph nodes (LN). These B7+CTLA4+ T cells were associated with an increased frequency of spontaneous apoptosis. Analysis of MHCII receptor expression on PBMC from HIV infected patients revealed a significant increase in MHCII+ expression on B7+ or CTLA4+ T cells. TUNEL analysis of B7+MHCII+ or CTLA4+MHCII+ compared to B7+MHCIIneg or CTLA4+MHCIIneg T cells revealed that the increased frequency of T cell apoptosis could almost exclusively be attributed to B7+MHCII+ and CTLA4+MHCII+ T cells, similar to our observations in the cat From these data we hypothesize that T: T interactions between CD4+ and CD8+ B7+CTLA4+MHCII+ T cells within the LN results in IL2 inhibition rendering them susceptible to cytokine deprived apoptosis.