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Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients
Joseph A. Kovacs, … , Dimiter S. Dimitrov, H. Clifford Lane
Joseph A. Kovacs, … , Dimiter S. Dimitrov, H. Clifford Lane
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2139-2148. https://doi.org/10.1172/JCI23196.
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Research Article AIDS/HIV

Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients

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Abstract

HIV infection leads to decreases in the number of CD4+ T lymphocytes and an increased risk for opportunistic infections and neoplasms. The administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound increases (often greater than 100%) in CD4 cell number and percentage. Using in vivo labeling with 2H-glucose and BrdU, we have been able to demonstrate that, although therapy with IL-2 leads to high levels of proliferation of CD4 as well as CD8 lymphocytes, it is a remarkable preferential increase in survival of CD4 cells (with half-lives that can exceed 3 years) that is critical to the sustained expansion of these cells. This increased survival was time-dependent: the median half-life, as determined by semiempirical modeling, of labeled CD4 cells in 6 patients increased from 1.7 weeks following an early IL-2 cycle to 28.7 weeks following a later cycle, while CD8 cells showed no change in the median half-life. Examination of lymphocyte subsets demonstrated that phenotypically naive (CD27+CD45RO–) as well as central memory (CD27+CD45RO+) CD4 cells were preferentially expanded, suggesting that IL-2 can help maintain cells important for host defense against new antigens as well as for long-term memory to opportunistic pathogens.

Authors

Joseph A. Kovacs, Richard A. Lempicki, Igor A. Sidorov, Joseph W. Adelsberger, Irini Sereti, William Sachau, Grace Kelly, Julia A. Metcalf, Richard T. Davey Jr., Judith Falloon, Michael A. Polis, Jorge Tavel, Randy Stevens, Laurie Lambert, Douglas A. Hosack, Marjorie Bosche, Haleem J. Issaq, Stephen D. Fox, Susan Leitman, Michael W. Baseler, Henry Masur, Michele Di Mascio, Dimiter S. Dimitrov, H. Clifford Lane

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Figure 3

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Slower decay of deuterium labeling in CD4 but not CD8 cells after later ...
Slower decay of deuterium labeling in CD4 but not CD8 cells after later cycles of IL-2. (A and C) Mean log decay shifted to the left for CD4 cells (A) but not CD8 cells (C) in 5 of 6 patients, indicating a longer average survival of CD4 cells (but not CD8 cells) following later IL-2 cycles (3 to 6) compared to earlier cycles (1 to 3). Patient 3 had an infusion of 2H-glucose before beginning IL-2 therapy (green diamonds), and patient 5 received a third infusion during his fourth IL-2 cycle (purple circles). The solid lines represent the fitting by the model equations. (B and D) The probability density function of the normal distribution of log d multiplied by the total source of labeled cells (S). Mean log decay rate constants for CD4/CD8 cells for the patients are, respectively: pt. 3, –0.59/0.06 (no IL-2), –0.33/–0.91 (cycle 1), –1.79/–0.68 (cycle 6); pt. 5, –1.03/–0.95 (cycle 1), –1.80/–1.30 (cycle 3), –1.86/–1.39 (cycle 4); pt. 6, –0.09/–2.05 (cycle 2), –1.73/–2.19 (cycle 4); pt. 7, –0.45/–1.01 (cycle 2), –0.94/–1.07 (cycle 5); pt. 8, –1.07/–2.18 (cycle 3), –2.30/–2.20 (cycle 4); pt. 10, –1.14/–0.95 (cycle 1), –0.66/–0.92 (cycle 3).

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