Enhanced IL-10 production by CD4 ⁺ T cells primed in IL-15Rα-deficient mice

In this study, we investigated the functional outcomes of CD4 ⁺ T cells primed in the absence of IL-15 transpresentation. Compared with their WT counterparts primed in WT mice, IL-15Rα KO CD4 ⁺ T cells primed in KO mice were found to exclusively overproduce IL-10 upon in vitro restimulation _. The comparable expression of IL-4 and Foxp3 in CD4 ⁺ T cells primed in the WT and IL-15Rα KO mice indicated that this was neither due to T _H2- nor Treg cell-differentiation. IL-10 overproduction was also observed when OVA-specific TCR transgenic CD4 ⁺ T (OT-II) cells were primed in KO mice, excluding an intrinsic deficiency of KO CD4 ⁺ T cells. To investigate the WT and KO microenvironment, DCs from both WT and IL-15Rα KO mice were compared. DCs from both backgrounds were indistinguishable in their steady-state survival and in their expression of MHC class II and costimulatory molecules CD80, CD86, and CD40. However, IL-15Rα KO DCs primed OT-II cells in vitro to produce higher levels of IL-10 upon their restimulation. Additionally, IL-15Rα KO DCs produced significantly more IL-10 upon activation, and IL-10 neutralization during DC-mediated in vitro priming abolished IL-10 overproduction by CD4 ⁺ T cells. Thus, IL-15Rα KO DCs provide an IL-10-enriched environment that preferentially primes CD4 ⁺ T cells for more IL-10 production, highlighting a regulatory role for IL-15 transpresentation in CD4 ⁺ T-cell priming.