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 develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b). Herein, we characterize these Bcl11b-independent γδ T cells in the periphery as CD5⁻NK1.1⁺ and Granzyme B⁺, and we 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, resembling their sequential appearance during development in the thymus. Bcl11b is essential for transition from the DN2a to the DN2b stage in the thymus. Hatano et al. find that CD5⁻NK1.1⁺ γδ T cells develop from the DN2a stage in a Bcl11b-independent manner and participate in host defense at an early stage after bacterial infection in periphery.