Infectious disease and host defense, Lymphocyte biology


Immunology and Infectious Disease


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. In this study, 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 naive CD8+ T cells. Lack of IL-4 responsiveness attenuates the capacity of CD8+ T cells to mount a robust response to lymphocytic choriomeningitis virus infection, with both quantitative and qualitative effects on effector and memory antigen-specific CD8+ T cells. Unexpectedly, we found that, although numerically rare, memory phenotype CD8+ T cells in IL-4Rα–deficient mice exhibited enhanced reactivity after in vitro and in vivo stimulation. Importantly, our data revealed that these effects of IL-4 exposure occur before, 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 cell cytokine, can sometimes promote rather than impair Th1 cell–type immune responses.


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Original Citation

Renkema, K. R., Lee, J. Y., Lee, Y. J., Hamilton, S. E., Hogquist, K. A., & Jameson, S. C. (2016). IL-4 sensitivity shapes the peripheral CD8(+) T cell pool and response to infection. JOURNAL OF EXPERIMENTAL MEDICINE, 213(7), 1319–1329.