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Abstract
INTERMITTENT IL-2 ADMINISTRATION IN HIV INFECTED PATIENTS LEADS TO A DECREASE IN CD4+ T CELL TURNOVER RATES
SERETI I, MARTINEZ-WILSON H, METCALF J, KOVACS J, LANE H
Background: Intermittent administration of IL-2 in HIV infected patients leads to a sustained expansion of the CD4+ but not CD8+ T cell pool although substantial increases in proliferation are seen in CD8+ as well as CD4+ T cells during an IL-2 cycle. In order to better define the mechanism of the CD4+ T cell expansion, the long-term effect of IL-2 on T cell proliferation was studied.
Methods: Frozen PBMCs collected at baseline and month12 from patients participating in a randomized controlled trial of IL-2 therapy were used. IL-2 patients (n=9) received antiretroviral therapy (limited to nucleoside analogues at the time of the study) and 5-day cycles of intravenous IL-2 every 8 weeks. Control patients (n=9) received antiretroviral therapy alone. CD4+ and CD8+ T cells were examined for expression of Ki67 nuclear antigen (marker of proliferation) along with expression of CD25 (alpha chain of the IL-2 receptor) and markers of memory vs naïve T cells (CD45RO and CD27).
Results: CD4 counts increased in IL-2 recipients from 442 to 1160c/ul while they decreased from 495 to 439c/ul in controls. A significant decrease in the percent of CD4+ T cells expressing Ki67 was observed in IL-2 treated patients (mean 10.7% at baseline vs 5.9% at month 12, p=0.0002) but not in controls (8.8% vs 8.2%). This decrease was noted in both naïve and memory CD4 subsets as well as in the CD25+ fraction of the CD4+ T cells (14.1% vs 6.7%, p=0.0001). Expression of Ki67 by CD8+ T cells did not change significantly from baseline in either group (IL-2:9.6% vs 8.5%, Controls:7.3% vs 7.9%).
Conclusion: The selective expansion of the CD4+ T cell pool induced by intermittent IL-2 is associated with a long-term decrease in CD4+ T cell proliferation, as measured by Ki67 expression, suggesting that enhanced survival of CD4+ T cells is important in maintaining this expansion. This effect of IL-2 is especially prominent in the CD25+ fraction of the CD4+ T cells that expands during IL-2 administration.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
103
Suggested Citation
"SERETII, et al.
INTERMITTENT IL-2 ADMINISTRATION IN HIV INFECTED PATIENTS LEADS TO A DECREASE IN CD4+ T CELL TURNOVER RATES.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
103"
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