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Session 44 Poster Presentations Lymphocyte Dynamics Session Day and Time: Wednesday 1:30 - 3:30 pm Room: Hall D

341
Intermittent IL-2 Administration to HIV-infected Patients Leads to Polyclonal Expansion of the CD4 T-cell Pool
I. Sereti*¹, L. Matthews¹, B. Hahn¹, T. Imamichi², S. Berg², R. Davey¹, H.C.Lane^1
1Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD and ²Sci Applications Intl Corp, Frederick, MD

Background: Intermittent administration of IL-2 cycles to HIV-infected patients (pts) leads to preferential expansion of CD4⁺/CD25⁺ cells, a large proportion of which have a naïve phenotype. It is currently unclear if IL-2 cycles induce polyclonal expansion with CD25 expression and proliferation of previously CD4⁺/CD25^- cells or if a limited expansion of CD4⁺/CD25⁺ cells occurs with each cycle leading to a more restricted CD4 T-cell repertoire.
Methods: We studied 8 HIV-1 infected pts receiving intermittent IL-2 and continuous HAART with median CD4 count 806 cells/ul (range: 354-1,057), median naïve CD4 count 261 cells/ul (range 90-354 cells/ul), 37% of which were CD25⁺, and viral load < 50 copies/mL at a median of 13 months (range 3-60) after an IL-2 cycle with: 1) immunophenotyping; 2) in vitro culture of CFSE-stained CD4⁺/CD25 depleted (< 5% CD25⁺) cells with 0 or 100 IU/ml of IL-2 for 5-7 days in the presence of CFSE-unstained CD4⁺/CD25⁺ cells, to allow distinction and tracking of cells that were CD4⁺/CD25^- at baseline; and 3) CDR3 size analysis of 24 TCR Vb subfamilies of bead separated naïve CD4⁺/CD25⁺, naïve CD4⁺/CD25^-, and memory CD4⁺ cells.
Results: After 5-7 days of in vitro stimulation with IL-2, there was a 5-fold increase of CD25 expression on CFSE-stained CD4⁺/CD25 depleted cells. This was accompanied by proliferation of 2%-6.5% of the cells (as detected by CFSE dilution) or 12% (as measured by intracellular staining with Ki67). CDR3 size analysis of separated CD4 subsets showed that naive CD4⁺/CD25⁺ cells had similar size distribution patterns to the naïve CD4/CD25^- cells that showed no skewing.
Conclusion: These in vitro and in vivo data suggest that intermittent cycles of IL-2 lead to CD25 expression and recruitment to proliferation of previously CD25 negative cells, thus preserving a polyclonal CD4 T-cell repertoire.

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