Session 25Oral Abstract Presentations Viral Pathogenesis Session Day and Time: Thursday 10 am - 12:30 pm Presentation Time: 10:30 Room: Ballroom A
122 T-cell Subsets that Harbor HIV In Vivo: Implications in HIV Pathogenesis J. Brenchley*, D. Ambrozak, B. Hill, M. Betts, M. Roederer, D. Douek, R. Koup Natl Inst of Hlth, Bethesda, MD
Background: HIV can infect non-dividing cells, but productive infection in vivo is facilitated by T-cell activation and/or proliferation. In vivo, CD4+ T-cells comprise many phenotypically and functionally distinct subsets. Infection within each of these subsets could occur with different efficiencies based upon various immunologic and virologic factors. In addition, infection of different CD8+ T-cell populations has been suggested. A clear understanding of which T-cells harbor HIV in vivo and whether T-cell activation/proliferation increases their infection is critical to understanding pathogenesis of HIV infection.
Methods: We utilized 11 parameter flow cytometry to define stringently and sort T-cell populations including naïve CD4+ and CD8+ T-cells, HIV-specific CD8+ T-cells, all other memory CD8+ T-cells, CD57- memory CD4+ T-cells and CD57+ memory CD4+ T-cells. We quantified and compared the amount of HIV DNA within each of these subsets by quantitative real-time PCR. Wilcoxon matched pairs test and Spearman’s rank tests were utilized for statistical comparisons.
Results: Memory CD4+ T-cells were found to be the most frequently infected subset with the CD57- memory subset being 10-fold more likely to be infected than the CD57+ memory subset. Naïve CD4+ T-cells are infrequently infected, their infection occurs predominantly in the subset which have proliferated in vivo, and their infection does not correlate with infection of memory CD4+ T-cells or naïve CD8+ T-cells. CD8+ T-cells are infrequently infected and memory CD8+ T-cells are infected more frequently than naïve CD8+ T-cells. Furthermore, HIV-specific CD8+ T-cells are not preferentially infected.
Conclusions: The majority of HIV-infected CD4+ T-cells in vivo are memory cells that can proliferate. Infection of developing thymocytes is not likely to lead to a substantial pool of infected naive T-cells. Infection of naïve CD4+ T-cells appears to occur during their ongoing turnover and infected naïve CD4+ T-cells do not become infected memory CD4+ T-cells. Therefore, these 2 subsets are infected under different conditions. Infection of CD8+ T-cells is rare. Activation of HIV-specific CD8+ T-cells by HIV does not lead to their preferential infection as reported for CD4+ T-cells. While HIV is able to infect non-dividing cells, HIV predominantly infects T-cells that are undergoing activation and/or proliferation in vivo.
