HIV-1-Infected T Cell Clone Defective in IL-2 Production and Ca2(+) Mobilizationafter CD3 Stimulation

摘要

Activation of HIV-1-infected T cells results in enhanced expression of viral geneproducts, especially when normal T cells are stimulated with mitogens such as PHA or via the Ag-specific TCR/CD3 complex. The programmed cellular events that follow such stimulation activate second messenger cascades involving Ca2+ influx and phosphatidylinositol hydrolysis, and give rise to lymphokine secretion, DNA synthesis, and finally proliferation. Inasmuch as many of the events leading to T cell activation occur under some of the same controls as events involved in the activation of HIV-1, cellular and biochemical dissection of these pathways should contribute to a better understanding of HIV-1 regulation. Cellular models of HIV-1 infection are useful for in vitro studies, especially when they contain the entire proviral genome and respond to physiologic stimuli. Cytokine and Ag-induced modification of HIV-1 expression have been observed in both acutely and chronically HIV-1-infected cellular models. Many experiments involving HIV-1-infected normal PBL are difficult to evaluate because of individual-to-individual variation, randomly mixed infections, and the unavailability of infected clones. Because of these limitations, tumor cell models are often desirable for in vitro HIV-1 T cell studies. However, the limited number of TCR/CD3+ bearing CD4+ tumor cell lines susceptible to HIV-1 also makes TCR activation studies difficult.