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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
Published April 6, 2017
Citation Information: JCI Insight. 2017;2(7):e90652. https://doi.org/10.1172/jci.insight.90652.
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Research Article Immunology Infectious disease

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

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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 8

Akt is required for IL-21–dependent CD4 T cell survival in vivo.

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Akt is required for IL-21–dependent CD4 T cell survival in vivo.
Purifie...
Purified naive clonotypic HA-specific CD4 T cells from WT or IL-21R–/– TCR-HA transgenic mice were stimulated with 40 ng/ml PMA and 500 ng/ml ionomycin for 24 hours in vitro. Stimulated cells were then infected with retrovirus-encoding dominant-negative (DN) Akt or constitutively activated (constitutive) Akt. The retroviral vectors carried GFP. Thus, the GFP+ cells after infection were selected by sorting. 5 × 104 GFP+ WT or IL21R–/– HA-specific T cells were transferred into Thy1.1 mice intravenously. Recipient mice were subsequently infected with 5 × 106 pfu VV by i.p. injection. Splenocytes were harvested for analysis 7 and 15 days after infection. (A) The percentage of GFP+Thy1.2+CD4+ cells among total CD4+ T cells. (B) The mean absolute numbers ± SEM of GFP+Thy1.2+CD4+ cells per spleen (n = 4 per group). Data are representative of 3 independent experiments.

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