CD5−NK1.1+ γδ T cells that develop in a Bcl11b-independent manner participate in early protection against infection

We recently found that a unique subset of innate-like γδ T cells develop from the DN2a-stage of the fetal thymus independent of the zinc-finger transcription factor B-cell leukemia/lymphoma 11b (Bcl11b). Herein we characterized these Bcl11b-independent γδ T cells in the periphery as CD5−NK1.1+ and Granzyme B+, and show that they are capable of producing interferon (IFN)-γ upon T cell receptor stimulation without Ca2+ influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues such as the liver. Bcl11b-independent CD5−NK1.1+ γδ T cells appeared and contributed to early protection before Bcl11b-dependent CD5+NK1.1− γδT cells following Listeria monocytogenes infection, recapitulating their appearance during thymic development. We analyzed global gene expression by comparing the transcriptome profiles of whole γδ T cells from CreRag1;Bcl11b flox/flox (flox/flox) mice, in which more than 99% were CD5−NK1.1+, prototypical Bcl11b-independent γδ T cells (CD5−NK1.1+ γδ T cells) and a prototypical Bcl11b-dependent γδ T cell subset (CD5+NK1.1− γδ T cells) sorted from the liver of WT mice.