527a-M.
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Increases in Naïve CD4+ T Cells in IL-2-Treated HIV Patients is Primarily Due to Peripheral Expansion of Existing Naïve CD4+ T Cells
V. Natarajan*1, R. A. Lempicki1, I. Sereti2, Y. Badralmma1, J. W. Adelsberger1, J. A. Metcalf2, R. Stevens1, M. W. Baseler1, J. A. Kovacs2, and H. C. Lane2
1SAIC, Frederick, MD and 2NIAID, NIH, Bethesda, MD
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Background: Intermittent IL-2 therapy in patients with HIV infection has been shown to preferentially increase the number of CD4+ T cells with a naïve phenotype. The underlying mechanism by which IL-2 treatment increases CD4+ cells is not fully understood. The increase could be due to the proliferation of existing cells or de novo production of naïve cells by thymus. In this report we have investigated the relative roles of peripheral expansion and thymic output in these CD4+ T cell expansions in IL-2 treated patients.
Methods: T-cell receptor rearrangement excision circle (TREC) levels and telomere restriction fragment length (TRFL) were measured in patients who had received 3-7 5-day IL 2 infusions during the study period of 12 months. Ex vivo BrdU incorporation, and Ki67 staining were used to measure the proliferation rates in purified T cells.
Results: 12 months after the initiation of IL-2 therapy the mean number of CD4+T cells increased from 721 to 1247 cells/muL while levels of TRECs declined from 43,504 to 23,733 copies/106 naïve T cells. A 7-fold increase in the percentage of Brdu positive cells and a 20- 40-fold increase in Ki-67 staining were observed in peripheral blood naïve CD4+ T cells during the 5 days of IL-2 administration. Average TRF length within the CD4 pool went from 6981 to 7153 base pairs following 1 year of IL-2 therapy.
Conclusions: These data strongly suggest that most of the increase in CD4+ cells associated with IL-2 treatment is due to peripheral expansion of existing naïve CD4+ T cells rather than by increased thymic output. The telomere length showed no significant change during the course of the study, indicating that these increases in CD4+ T cells occur without compromising the potential of these cells for further division.
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