Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance

Michiko Shimoda, Faith Mmanywa, Sunil K. Joshi, Tao Li, Katsuya Miyake, Jeanene Pihkala, Jonathan A. Abbas, Pandelakis A. Koni

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Although the importance of MHC class II (MHC-II) in acute homeostatic proliferation of regulatory T (Treg) cells has been established, we considered here the maintenance and state of Treg cells in mice that are almost completely devoid of MHC-II in their periphery but still make their own CD4 T cells and Treg cells. The latter was accomplished by conditional deletion of a loxP-flanked MHC-II β-chain allele using a TIE2Cre transgene, which causes a very high degree of deletion in hemopoietic/endothelial progenitor cells but without deletion among thymic epithelial cells. Such conditional MHC-II-deficient mice possess their own relatively stable levels of CD4 +CD25+ cells, with a normal fraction of Foxp3+ Treg cells therein, but at a level ∼2-fold lower than in control mice. Thus, both Foxp3low/- CD4+CD25+ cells, said to be a major source of IL-2, and IL-2-dependent Foxp3+ Treg cells are reduced in number. Furthermore, CD25 expression is marginally reduced among Foxp3+ Treg cells in conditional MHC-II-deficient mice, indicative of a lack of MHC-II-dependent TCR stimulation and/or IL-2 availability, and IL-2 administration in vivo caused greatly increased cell division among adoptively transferred Treg cells. This is not to say that IL-2 can cause Treg cell division in the complete absence of MHC-II as small numbers of MHC-II-bearing cells do remain in conditional MHC-II-deficient mice. Rather, this suggests only that IL-2 was limiting. Thus, our findings lend support to the proposal that Treg cell homeostasis depends on a delicate balance with a population of self-reactive IL-2-producing CD4+CD25+ cells which are themselves at least in part MHC-II-dependent.

Original languageEnglish (US)
Pages (from-to)6503-6511
Number of pages9
JournalJournal of Immunology
Volume176
Issue number11
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Shimoda, M., Mmanywa, F., Joshi, S. K., Li, T., Miyake, K., Pihkala, J., Abbas, J. A., & Koni, P. A. (2006). Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance. Journal of Immunology, 176(11), 6503-6511. https://doi.org/10.4049/jimmunol.176.11.6503