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

• Published in: European journal of immunology Vol. 41; no. 11; pp. 3146 - 3156
• Main Authors: Chow, Kai‐Ping N., Lee, Jan‐Mou, Qiu, Jian‐Tai, Liao, Shuen‐Kuei, Lin, Shih‐Chieh, Hsu, Shuo‐Lun, Wu, Ning‐Ning, Lin, Yen‐Fu, Wu, Tzong‐Shoon
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.11.2011
• Subjects: Animals; CD4+ T‐cell differentiation; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Separation; DCs; Flow Cytometry; IL‐10; IL‐15 transpresentation; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; Interleukin-15 Receptor alpha Subunit - deficiency; Interleukin-15 Receptor alpha Subunit - immunology; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141746

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 TH2‐ 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.