Migration and chemokine receptor expression of regulatory T cells during acute viral infection

Abstract

Regulatory T cells play an important role in maintenance of immune homeostasis and tolerance through regulation of excessive immune response. As well as suppressive potential but also migration ability of Treg cells is also a crucial factor that promotes their role. However, mechanism underlying this migration of Treg cells during acute viral infection has not been specifically studied. In this study, we focused on chemokine receptors that influence Treg cells to move to the target site where severe immune response occurring.

During lethal influenza infection, we observed increased frequency and absolute count of Treg cells in the lungs. To determine the chemokine receptors related to the appropriate localization of Treg cells, we analyzed various chemokine receptors on lung-localized Treg cells and CCR2, CCR5 and CXCR3 were chosen as candidates. Furthermore, we confirmed that three chemokine receptors were related to migration of Treg cells through performing in vitro migration assay and adoptive transfer experiment using chemokine receptor deficient mice.

During acute hepatitis A infection, expression of CCR5 was up-regulated on peripheral circulating Treg cells so we denoted them as candidates participating in migration of Treg cells to liver. In addition, the levels of chemokine related to CCR5 were higher than healthy controls in patients’ serum. Lastly, we observed that the highly expression of $CCR5^+$ on Treg cells located in liver during acute hepatitis A infection. With our present study, we investigated for the first time the expression of various chemokine receptors involved in the migration of Treg cells during acute viral infection. We suggest that the expression of CCR2, CCR5 and CXCR3 has a critical role in localization of Treg cells into the flu-infected lungs. Furthermore, in case of acute hepatitis A virus infection, we purpose that CCR5 seems to participate in migration of Treg cells to the liver.