Identification of cellular sources of IL-2 needed for regulatory T cell development and homeostasis

David L. Owen, Shawn A. Mahmud, Kieng B. Vang, Ryan M. Kelly, Bruce R. Blazar, Kendall A. Smith, Michael A. Farrar

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The cytokine IL-2 is critical for promoting the development, homeostasis, and function of regulatory T (Treg) cells. The cellular sources of IL-2 that promote these processes remain unclear. T cells, B cells, and dendritic cells (DCs) are known to make IL-2 in peripheral tissues. We found that T cells and DCs in the thymus also make IL-2. To identify cellular sources of IL-2 in Treg cell development and homeostasis, we used Il2 FL/FL mice to selectively delete Il2 in T cells, B cells, and DCs. Because IL-15 can partially substitute for IL-2 in Treg cell development, we carried out the majority of these studies on an Il15 -/- background. Deletion of Il2 in B cells, DCs, or both these subsets had no effect on Treg cell development, either in wild-type (WT) or Il15 -/- mice. Deletion of Il2 in T cells had minimal effects in WT mice but virtually eliminated developing Treg cells in Il15 -/- mice. In the spleen and most peripheral lymphoid organs, deletion of Il2 in B cells, DCs, or both subsets had no effect on Treg cell homeostasis. In contrast, deletion of Il2 in T cells led to a significant decrease in Treg cells in either WTor Il15 -/- mice. The one exception was the mesenteric lymph nodes where significantly fewer Treg cells were observed when Il2 was deleted in both T cells and DCs. Thus, T cells are the sole source of IL-2 needed for Treg cell development, but DCs can contribute to Treg cell homeostasis in select organs.

Original languageEnglish (US)
Pages (from-to)3926-3933
Number of pages8
JournalJournal of Immunology
Volume200
Issue number12
DOIs
StatePublished - Jun 15 2018

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) Grant P30CA77598 to the University of Minnesota Flow Cytometry Resource. D.L.O., S.A.M., and K.B.V. were supported by an NIH T32 grant (T32 AI07313). S.A.M. was also supported by NIH Grant F30 DK096844. B.R.B. was supported by NIH Grant R01 HL11879. M.A.F. is supported by NIH Grants R56AI113138 and R01 AI124512 and by the University of Minnesota Masonic Cancer Center.

Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.

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