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
View: Text | PDF
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

×

Figure 3

The activation of CD4 T cells is independent of IL-21 signaling.

Options: View larger image (or click on image) Download as PowerPoint
The activation of CD4 T cells is independent of IL-21 signaling. 5 × 105...
5 × 105 purified naive clonotypic CD4 T cells from WT or IL-21R–/– TCR-HA transgenic mice (Thy1.2+) were transferred into Thy1.1+ congenic recipients that were subsequently infected with VV-HA (5 × 106 pfu, i.p., +VV). Some mice were left uninfected (Naive). (A and B) Twenty-four hours after infection, splenocytes were harvested and stained with antibodies to CD4, Thy1.2, and the activation markers CD44 or CD69. (A) FACS plots and the percentages of CD44hi and CD69hi. (B) Mean absolute numbers ± SEM of CD44hi and CD69hi (n = 4 per group). (C) Three days after infection, in vivo division of CFSE-labeled clonotypic cells in the spleen was analyzed, and the percentages of CFSE-positive cells are shown. (D and E) Seven days after infection, splenocytes were stained with anti-CD4, anti-Thy1.2, and anti–IFN-γ intracellularly. (D) FACS plots and the percentages of IFN-γ–producing clonotypic cells. (E) Mean absolute numbers ± SEM of IFN-γ–producing clonotypic cells among clonotypic CD4 T cells (n = 4 per group). Data shown are representative of 3 independent experiments.