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

Abstract

Several gene deficiency models promote the development of “innate CD8+ T cells” that have diverse TCRs, but display a memory phenotype and rapidly produce cytokines. We here demonstrate that similar cells develop in Kruppel-Like Factor 2 (KLF2) deficient mice. However, this is not due to intrinsic deficiency in KLF2, but rather to interleukin 4 (IL-4) produced by an expanded population of T cells expressing the PLZF transcription factor. The development of innate CD8+ T cells in ITK and CBP transcription factor deficient mice is also attributable to this IL-4-dependent mechanism. Finally, we show that the same mechanism drives innate CD8+ T cell differentiation in BALB/c mice. These findings reveal a novel mechanism of regulation of CD8+ T cells via PLZF+ T cell production of IL-4.