IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection

Abstract

Abstract Previous studies have revealed that a population of innate memory CD8+ T cells is generated in response to IL-4, first appearing in the thymus and bearing high expression levels of Eomesodermin (Eomes) but not T-bet. However, the antigen specificity and functional properties of these cells is poorly defined. Here we show that IL-4 regulates not only the frequency and function of innate memory CD8+ T cells but also regulates Eomes expression levels and functional reactivity of naïve CD8+ T cells. Lack of IL-4 responsiveness attenuates the capacity of CD8+ T cells to mount a robust response to LCMV infection, with both quantitative and qualitative effects on effector and memory antigen specific CD8+ T cells. Importantly, our data revealed that these effects of IL-4 exposure occur prior to, not during infection. Together, these data show that IL-4 influences the entire peripheral CD8+ T cell pool, influencing expression of T-box transcription factors, functional reactivity and the capacity to respond to infection. These findings indicate that IL-4, a canonical Th2 cytokine, can sometimes promote rather than impair Th1-type immune responses.