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| Abstract |
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Session 17
Symposium T-Cell Turnover and Thymic Function Session Time: Tuesday, 2 - 4 pm Room 6E |
Background: Understanding the effects of HIV on lymphocyte turnover will help provide insights into the immunopathogenesis of HIV infection. Direct examination of lymphocyte turnover by in vivo labeling with bromodeoxyuridine (BrdU) allows even small populations of proliferating cells to be followed longitudinally. Using BrdU labeling in 17 patients, we have shown that proliferation of both CD4+ and CD8+ T lymphocytes is initially higher in lymph nodes than in blood, but that there is a rapid equilibration of labeled cells between these compartments. Methods: By mathematical modeling we identified rapidly and slowly proliferating subpopulations of both CD4+ and CD8+ T lymphocytes. The percentage of labeled cells in the rapidly proliferating pool correlated significantly with plasma HIV RNA levels for both CD4+ (r=0.77, p<0.001) and CD8+ (r=0.81, p<0.001) T cells, suggesting that a major effect of HIV is to increase lymphocyte proliferation by driving cells into this rapidly proliferating pool. Results: In support of this, we found a significant decrease in the percentage of labeled cells in the rapidly proliferating pool for both CD4+ (p=0.03) and CD8+ (p<0.001) T lymphocytes. In 6 patients within 2-6 months following the initiation of highly active antiretroviral therapy. Neither plasma viral levels nor therapy had an effect on the percentage of labeled cells in the slowly proliferating pool, in which the cells undergoing homeostatic proliferation likely reside. Decay rates of the 2 populations were similarly unrelated to either viral load or therapy. Conclusions: These findings demonstrate that HIV drives CD4 and CD8 lymphocyte proliferation and death by inducing entry into the rapidly proliferating subpopulation of cells, but provide no evidence to suggest that HIV impairs T cell production. |
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©2002 9th Conference on Retroviruses and Opportunistic Infections |
