| First Author | Renkema KR | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 7 | Pages | 1319-29 |
| PubMed ID | 27298446 | Mgi Jnum | J:236254 |
| Mgi Id | MGI:5805592 | Doi | 10.1084/jem.20151359 |
| Citation | Renkema KR, et al. (2016) IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection. J Exp Med 213(7):1319-29 |
| abstractText | 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-4Ralpha-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. |
