IL-7, but not thymic stromal lymphopoietin (TSLP), during priming enhances the generation of memory CD4⁺ T cells

Multiple activation signals (including antigen, co-stimulation, and cytokines) during T-cell priming affect the subsequent generation of memory T cells, whose survival is maintained by IL-7 and IL-15. Since the IL-7 receptor is highly expressed not only on the surface of memory T cells but also on naïve T cells, we propose that early exposure to IL-7 during priming of naïve T cells may promote their survival, and thus enhances the generation of memory cells. To test this hypothesis, TCR transgenic OT-II CD4⁺ T cells were stimulated in vitro with OVA_323-339 peptide presented by syngeneic antigen-presenting cells (APCs). IL-7 or an IL-7 like cytokine, thymic stromal lymphopoietin (TSLP), was added at the initial 2-day cultivation stage. We found that a short exposure to IL-7 or TSLP during priming did not affect activation, proliferation, and glucose uptake by CD4⁺ T cells compared to controls when examined on culture day 6. However, the same 6-day cultures showed that IL-7 (but not TSLP) significantly decreased the frequency of apoptotic CD4⁺ T cells compared to controls. More importantly, an adoptive transfer of the 6-day primed OT-II T cells into CD45.1⁺ congenic mice demonstrated that IL-7 (but not TSLP) elevated by 3- and 4-fold the number of transferred CD4⁺ T cells in spleen (p<0.05) and lymph nodes (p<0.05), respectively, compared to controls. Almost all transferred CD4⁺ T populations displayed phenotypes of effector (CD44⁺CD62L^-) or central (CD44⁺CD62L⁺) memory T cells. We thus conclude that exposure of CD4⁺ T cells to IL-7 during priming results in an increased frequency of CD4⁺ memory T cells.