Background: Intermittent IL-2 administration in HIV+ patients leads to an expansion of the CD4+ T-cell pool with a selective increase in naïve CD4+ T cells. To better define the characteristics and origins of the CD4+ T-cell expansions seen in the setting of IL-2, the phenotype and TREC content of these cells were studied in detail.

Methods: 7 HIV+ patients were studied. These patients had CD4+ T-cell numbers that had increased from a median of 643-1198 cells/<greek>mu</greek>L following IL-2.  Overall, 42% of the CD4+ T cells were naïve (CD45RO-/CD27+) and 58% of these naïve CD4+ cells expressed CD25 (range 35-84%). After purification of naïve CD4+/CD25+ and naïve CD4+/CD25- T-cell subsets by bead separation or sorting, TREC quantitation by real-time PCR by the cell lysis method was performed. Paired comparisons were done by the paired signed rank test (nonparametric).

Results: Naïve CD4+/CD25+  T cells, when compared to naïve CD4+/CD25- T cells expressed lower levels of CD38 (68% vs 96%) and CD132 ( chain of the IL-2R, 5% vs 23%) and higher levels of CD95 (73% vs 41%), TNFRII (61% vs 5.5%), and surface and intracellular CTLA4 (7.7% vs 1.3%, 52.5% vs 20%) (p <0.05 for all comparisons). Expression of CD27, CD28, L-selectin, CD69, CD122 ( chain of the IL-2R), HLA-DR, CXCR4, CCR5 and intracellular Ki67 and bcl-2 were similar in the two subsets. TREC content in the naïve CD4+ pool decreased by 3- to 6-fold with IL-2 therapy and the TREC levels of the naïve CD4+/CD25+ cells were significantly lower than the TREC levels of the CD4+/CD25- cells (6,638 copies/10⁶ cells vs 65,038 copies/10⁶ cells, p=0.02), thus suggesting a higher proliferative history for these cells.

Conclusions: Intermittent IL-2 in HIV-infected patients leads to expansion of a unique population of naïve CD4+ T cells expressing CD25 that have a distinct phenotype and a significantly lower TREC content compared to naïve CD4+/CD25- cells. These data suggest that these cells do not represent recent thymic emigrants but rather the product of peripheral T-cell expansion.