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

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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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Regulatory T-Lymphocytes
Maintenance
Interleukin-2
Cell Division
Transgenes
Homeostasis
Epithelial Cells
Alleles
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance. / Shimoda, Michiko; Mmanywa, Faith; Joshi, Sunil; Li, Tao; Miyake, Katsuya; Pihkala, Jeanene; Abbas, Jonathan A.; Koni, Pandelakis A.

In: Journal of Immunology, Vol. 176, No. 11, 01.06.2006, p. 6503-6511.

Research output: Contribution to journalArticle

Shimoda, M, Mmanywa, F, Joshi, S, Li, T, Miyake, K, Pihkala, J, Abbas, JA & Koni, PA 2006, 'Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance', Journal of Immunology, vol. 176, no. 11, pp. 6503-6511. https://doi.org/10.4049/jimmunol.176.11.6503
Shimoda, Michiko ; Mmanywa, Faith ; Joshi, Sunil ; Li, Tao ; Miyake, Katsuya ; Pihkala, Jeanene ; Abbas, Jonathan A. ; Koni, Pandelakis A. / Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance. In: Journal of Immunology. 2006 ; Vol. 176, No. 11. pp. 6503-6511.
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