HIV alters the function of Cytotoxic T- Lymphocytes (CTL) and Antigen presenting cells (APC)
The CD8+ T cell killing of HIV infected target cells are mediated through secretion of granzymes and perforin. The CD4+ T cell secreted cytokines IL-2 and IFN-γ are known to play a major role in CD8+ T cell survival and function. In this work, it has been observed that endogenous IFN-γ does regulate the expression of perforin and granzymes. In support of this hypothesis, the addition of rIFN-γ to CD8+ T cells showed an increased expression of granzymes and perforin. Next, the effect of HIV proteins Tat and Nef were tested on the effector functions of macrophages and T cells. It was observed that Tat down- regulates the expression of CD40, IL-12 and TNF-α, ut no effect was observed on the expression of TGF-β. These results suggest that Tat may down- regulate the CD40 expression on macrophages, hich would result in the inhibition of CD40 induced IL-12 and it may result in diminished IFN-γ producing Th1 cells. The effect of Tat and Nef were also tested on the expression of perforin and granzymes from T cells. It was observed that Tat and Nef seem to have a synergistic effect with anti- CD3 in the expression of granzymes and perforin. In addition, the expression profile of various cytokines were tested on HIV infected and uninfected human PBMCs. The observations suggest that HIV infection results in skewing of T cells response towards a Th2 type, as it is evident by the increased expression of IL-4, IL-10 and decreased expression of IFN-γ and IL-2.
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