IL-21 is required for CD4 memory formation in response to viral infection
Yuqing Yuan, Yiping Yang, Xiaopei Huang
Yuqing Yuan, Yiping Yang, Xiaopei Huang
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Research Article Immunology Infectious disease

IL-21 is required for CD4 memory formation in response to viral infection

Abstract

IL-21 has been shown to play an important role in the CD8 T cell response during acute and chronic viral infections. However, the role of IL-21 signaling in the CD4 T cell response to viral infection remains incompletely defined. In a model of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T cells was critical for the formation of memory CD4 T cells in vivo. We further reveal that IL-21 promoted CD4 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 signaling pathways. In addition, the activation of Akt is also required for IL-21–dependent survival of CD4 T cells in vivo. These results identify a critical role for intrinsic IL-21 signaling in CD4 T cell survival and memory formation in response to viral infection in vivo and may provide insights into the design of effective vaccine strategies.

Authors

Yuqing Yuan, Yiping Yang, Xiaopei Huang

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Figure 5

IL-21 signaling promotes activation of STAT1 and STAT3.

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IL-21 signaling promotes activation of STAT1 and STAT3. (A and B) Purifi...
(A and B) Purified polyclonal CD4 T cells were cultured for 1 hour in medium alone (Medium) or medium supplemented with recombinant murine IL-21 (+ IL21). (A) Cells were stained with anti-STAT1, anti-pSTAT1, anti-STAT3, or anti-pSTAT3 intracellularly. (B) Mean percentages ± SEM of STAT1-, pSTAT1-, STAT3-, or pSTAT3-positive cells (n = 4 per group). (C and D) 5 × 105 purified naive clonotypic CD4 T cells from WT or IL-21R–/– TCR-HA transgenic mice (Thy1.2+) were transferred to Thy1.1+ congenic recipients that were subsequently infected with VV-HA (5 × 106 pfu). Some mice were left uninfected (Naive). (C) Seven days after infection, splenocytes were stained with anti-CD4 and anti-Thy1.2 as well as anti-pSTAT1, anti-pSTAT3, anti-STAT1, anti-STAT3, or an isotype control intracellularly. (D) Mean percentages ± SEM of pSTAT1+ and pSTAT3+ among clonotypic CD4 T cells (n = 4 per group). Data are representative of 3 independent experiments.