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

First Author  Chow KP Year  2011
Journal  Eur J Immunol Volume  41
Issue  11 Pages  3146-56
PubMed ID  21874651 Mgi Jnum  J:179518
Mgi Id  MGI:5302600 Doi  10.1002/eji.201141746
Citation  Chow KP, et al. (2011) Enhanced IL-10 production by CD4+ T cells primed in IL-15Ralpha-deficient mice. Eur J Immunol 41(11):3146-56
abstractText  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-15Ralpha 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-15Ralpha KO mice indicated that this was neither due to T(H) 2- 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-15Ralpha 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-15Ralpha KO DCs primed OT-II cells in vitro to produce higher levels of IL-10 upon their restimulation. Additionally, IL-15Ralpha 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-15Ralpha 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.
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