Keywords
Infectious disease and host defense, Lymphocyte biology
Disciplines
Immunology and Infectious Disease
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. 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.
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. https://doi.org/10.1084/jem.20151359
ScholarWorks Citation
Renkema, Kristin R.; Lee, June-Yong; Lee, You Jeong; Hamilton, Sara E.; Hogquist, Kristin A.; and Jameson, Stephen C., "IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection" (2016). Peer Reviewed Articles. 38.
https://scholarworks.gvsu.edu/bms_articles/38
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