The transcription factor PLZF controls the development of mouse and human innate T cells (64.6)

Abstract

Abstract Natural killer T cells (NKT cells) have an innate immunity-like rapidity of response and the capacity to modulate effector functions of other cells. We have shown that NKT cells express the BTB-ZF transcriptional regulator PLZF. In the absence of PLZF, NKT cells developed, but lacked many innate T cell features. We have also shown that PLZF expression is not restricted to NKT cells, but is also expressed by a subset of NKT cell-like γδ T cells. Interestingly, TCR signal strength and expression of Id3 appear to control the frequency of PLZF-expressing γδ T cells. In human T cells PLZF is expressed in NKT cells, γδ T cells and, unexpectedly, in a population of CD8+ T cells. Analysis of T cells from the only known human with a biallelic loss of functional PLZF demonstrates that the development of invariant NKT cells and other PLZF-expressing T cell subsets is dependent upon expression of PLZF. The PLZF-expressing CD8+ T cells are functionally distinct from both conventional T cells and from invariant NKT cells. Furthermore, this subset of T cells is expanded in the peripheral blood of patients with metastatic melanoma; however it is greatly diminished in that of patients with autoimmune disease. Therefore, the expression of PLZF defines a new human T cell population that is differentially regulated in response to different types of immune stress. Furthermore, these data highlight important differences between the human and mouse immune system.