Browsing by Author "Hewitt, Tracy P."

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    Cellular and Molecular Mechanisms Involved with Feline CD8+ T Cell Mediated Anti-FIV Activity
    (2006-03-02) Hewitt, Tracy P.; Dr. Wayne Tompkins, Committee Chair
    A population of activated CD8+ T cells that express the B7.1 (CD80) and B7.2 (CD86) costimulatory molecules and their ligand CTLA4 exist in the blood of asymptomatic FIV-infected cats. As evidence of CD8+ T cell mediated anti-FIV activity, coculture of CD8+ depleted-PBMC with FCD4E cells resulted in a significant increase in FIV p24 levels as compared to total PBMC cocultures. This anti-FIV activity was not overridden by the addition of either rhIL-2 or ConA. All cats were infected either intravenously or vaginally. There was no correlation between the route of infection and the presence of CD8+ T cell-mediated antiviral activity. Nonsuppressor cats had a higher number of viral RNA molecules per milliliter of plasma than the suppressor cats. PBMC from suppressor cats had a higher percentage of CD8+ CD25+ cells as compared to nonsuppressor cats. Both CD8+ CD25+ and CD8+ CD25- subsets inhibited FIV replication. CD8+ cells from suppressor cats also had an increased in the frequency of B7.1+ CD8+ cells with a low expression of the CD8β chain, suggesting that the CD8+ anti-FIV cells express the activation phenotype, CD8+ βlo B7.1+. Depletion of B7.1+ cells from PBMC of suppressor cats resulted in increased viral replication similar to depletion of CD8+ cells. CD8+B7.1+ and CD8+B7.1- subsets cocultured with infected CD4+ T cells revealed that the antiviral activity reside primarily in CD8+ B7.1+ subset. The presence of CD8+ antiviral cells lead to a decrease in the number of FIV RNA molecules per 106 CD4+ T cells in suppressor cats with no appreciable difference in the expression of IL-2 mRNA levels from either group of cats. The results of this study showed a strong correlation between the presence of CD8+ T cell anti-FIV activity, a reduction in viremia, low expression of the CD8β chain and expression of B7.1 costimulatory molecule on CD8+ T cells in suppressor cats suggesting that CD8+ βlo B7.1+ antiviral cells may play a major role in controlling FIV replication in vivo.