Expansion of melanoma-specific lymphocytes in alternate gamma chain cytokines: gene expression variances between T cells and T-cell subsets exposed to IL-2 versus IL-7/15.

Abstract

We have previously demonstrated that expansion of activated tumor-sensitized T cells in interleukin (IL)-7/15 results in greater expansion and anti-tumor activity than expansion in IL-2. We sought to determine whether T cells exposed to IL-2 versus IL-7/15 exhibited distinct gene expression patterns. Lymphocytes were harvested from Pmel-1 mice immunized with B16-GMCSF melanoma cells, activated in vitro, and cultured in IL-2 or IL-7/15 for 1, 3 or 6 days. T cells were harvested and analyzed by microarray, real-time quantitative polymerase chain reaction (RT-QPCR), or sorted into T cell subsets and analyzed. We found significant differences in gene expression for T cells cultured in IL-2 vs. IL-7/15, starting at day 3. This was not a function of subset differentiation; when T cell were divided into subsets, the central memory (TCM), effector memory (TEM) and effector (TE) T cells cultured in the IL-2 more closely resembled each other than the identical phenotypic subset exposed to IL-7/15. Thus, the differences in gene expression induced by culture in IL-2 versus IL-7/15 do not merely reflect differences in frequency of TCM vs. TEM vs. TE cells, but rather reflect that the gene expression of those T cell subsets when exposed to different cytokines are fundamentally different.