The subclassification of immunology into innate and adaptive immunity is challenged by innate-like T lymphocytes that use innate receptors to respond rapidly to stress despite expressing T cell antigen receptors (TCRs), a hallmark of adaptive immunity. In studies that explain how such cells can straddle innate and adaptive immunity, we found that signaling via antigen receptors, whose conventional role is to facilitate clonal T cell activation, was critical for the development of innate-like T cells but then was rapidly attenuated, which accommodated the cells' innate responsiveness. These findings permitted the identification of a previously unknown innate-like T cell subset and indicate that T cell hyporesponsiveness, a state traditionally linked to tolerance, may be fundamental to T cells entering the innate compartment and thereby providing lymphoid stress surveillance.
γδ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ T cells. Thus, MyD88 deficiency severely impaired the response to malaria infection of CD27(−), IL-17A–producing γδ T cells, but not of IFN-γ–producing γδ cells. Instead, the latter compartment was severely contracted by ablating CD27, which synergizes with TCRγδ in the induction of antiapoptotic mediators and cell cycle-promoting genes in CD27(+), IFN-γ–secreting γδ T cells. Hence, innate versus adaptive receptors differentially control the peripheral pool sizes of discrete proinflammatory γδ T cell subsets during immune responses to infection.
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