Innate-like T cells straddle innate and adaptive immunity by altering antigen-receptor responsiveness

Abstract

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.