Abstract

E-mail Abstract Author Add To Itinerary Session Search Abstracts Program

Session 25 Oral Abstract Session Immunology Session Time: Wednesday, 10 am - 12:30 pm Room 6C

10:30   103. Prolonged and Preferential Survival of CD4+ T Lymphocytes in HIV-Infected Patients Receiving IL-2 Therapy J. Kovacs*1, R. A. Lempicki2, I. A. Sidorov4, J. W. Adelsberger2, G. Kelly1, J. A. Metcalf3, R. T. Davey3, J. Falloon3, M. A. Polis3, J. Tavel3, R. Stevens2, L. Lambert2, D. Hosack2, H. J. Issaq2, S. Fox2, S. Leitman1, M. W. Baseler2, H. Masur1, D. S. Dimitrov4, and H. C. Lane3 1Clin. Ctr., 3NIAID, and 4NCI, NIH, Bethesda, MD; and 2SAIC, Frederick, MD Background: Intermittent interleukin-2 (IL-2) therapy can lead to substantial and sustained increases in CD4+ T-cell numbers in HIV-infected patients without increasing CD8+ T-cell numbers. While increased proliferation has been identified as one possible mechanism leading to the increase in CD4+ cells, the effects of IL-2 on proliferation and survival of lymphocyte subsets has not been well studied. Methods: To examine both lymphocyte proliferation and survival, 3 patients receiving no IL-2 (controls) and 2 patients who were responders to intermittent IL-2 therapy and who received a single 5-day cycle of IL-2 received 5-day infusions of 2H-glucose. Proliferation and survival of CD4 and CD8 cells were determined by measuring deuterium incorporation into DNA of both CD4 and CD8 cells at multiple time-points after an IL-2 cycle. Results: Proliferation of both CD4 and CD8 cells was dramatically increased in the patients receiving IL-2: peak labeling was increased >10-fold (mean 69% and 48% respectively, vs 4.7% and 4.2%, respectively, in controls). A 2-phase decay for loss of labeled DNA was seen in both cell populations for all patients. In control patients, the calculated terminal half-life of labeled CD4+ cells was approximately 0.7 years. For the 2 patients receiving IL-2, survival of the proliferating CD4+ cells was substantially longer, with terminal half-lives of 2.9-4.5 years. CD8+ cells showed a more rapid decay, with a mean terminal half-life of 0.23 years for controls and 0.8-0.9 years for the patients receiving IL-2. In the latter patients, 35-48% of CD4+ cells were still labeled 2 years after the IL-2 cycle, compared to 4 to 18% of CD8+ cells. Conclusions: Intermittent IL-2 therapy leads to profound levels of proliferation of both CD4+ and CD8+ lymphocytes. The expansion of CD4+ cells in patients responding to IL-2 is due to a preferential expansion of CD4+ cells relative to CD8+ cells together with an unexpectedly prolonged survival of these expanded cells.

©2002 9th Conference on Retroviruses and Opportunistic Infections