T cells expressing the transcription factor PLZF regulate the development of memory-like CD8+ T cells.
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.
Weinreich
Michael A
MA
The Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Odumade
Oludare A
OA
Jameson
Stephen C
SC
Hogquist
Kristin A
KA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D048708:Cell Growth Processes / Q000276:immunology; D002678:Chimera; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell; C513267:Zbtb16 protein, mouse; D015847:Interleukin-4