T cells expressing the transcription factor PLZF regulate the development of memory-like CD8+ T cells

Michael A. Weinreich, Oludare A. Odumade, Stephen C. Jameson, Kristin A. Hogquist

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

Several gene-deficiency models promote the development of innate CD8 + T cells that have diverse T cell antigen receptors (TCRs) but have a memory phenotype and rapidly produce cytokines. We demonstrate here that similar cells developed in mice deficient in the transcription factor KLF2. However, this was not due to intrinsic deficiency in KLF2 but instead was due to interleukin 4 (IL-4) produced by an expanded population of T cells expressing the transcription factor PLZF. The development of innate CD8+ T cells in mice deficient in the tyrosine kinase Itk and coactivator CBP was also attributable to this IL-4-dependent mechanism. Finally, we show that the same mechanism drove the differentiation of innate CD8+ T cells in BALB/c mice. Our findings identify a previously unknown mechanism of regulation of CD8+ T cells via the production of IL-4 by PLZF + T cells.

Original languageEnglish (US)
Pages (from-to)709-716
Number of pages8
JournalNature immunology
Volume11
Issue number8
DOIs
StatePublished - Aug 2010

Bibliographical note

Funding Information:
We thank F. Finkelman (University of Cincinnati) for B6 Il4ra−/− mice; D. Kioussis (National Institute for Medical Research, London) for Vav-Cre mice; J. Lingrel (University of Cincinnati) for Klf2fl/fl mice; R. Proia (National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health) for S1pr1fl/fl mice; Y. Shimizu (University of Minnesota) for Itk−/− mice; R. Braun (Jackson Laboratory) for PLZFlu/lu mice; D. Masopust (University of Minnesota) for SMARTA TCR-transgenic mice; P. Brindle (St. Jude Children’s Research Hospital) for Cbpfl/flLck-Cre bone marrow; X. Ding, J. Vevea, J. Reyes and C. Mora-Solano for technical assistance; and L. Berg and P. Schwartzberg for discussions. H. O’Donnell did initial experiments with Il4ra−/− mice. Supported by the US National Institutes of Health (R01 AI35296 to K.A.H., R37 AI38903 to S.C.J., and T32 AI007313 to M.A.W.) and the University of Minnesota (M.A.W.).

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