期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 41, 期 11, 页码 3146-3156出版社
WILEY
DOI: 10.1002/eji.201141746
关键词
CD4(+) T-cell differentiation; DCs; IL-15 transpresentation; IL-10
类别
资金
- National Science Council, Taiwan, ROC [93-2320-B-182-052]
- Chang Gung Memorial Hospital [CMRPD16029]
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-15R alpha 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-15R alpha 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-15R alpha 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-15R alpha KO DCs primed OT-II cells in vitro to produce higher levels of IL-10 upon their restimulation. Additionally, IL-15R alpha 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-15R alpha 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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