A function for IL-7R for CD4 CD25 foxp3 T regulatory cells

The IL-2/IL-2R interaction is important for development and peripheral homeostasis of T regulatory (T _reg) cells. 1L-2- and IL-2R-deficient mice are not completely devoid of Foxp3 ⁺ cells, but rather lack population of mature CD4 ⁺CD25 ⁺Foxp3 ^hieh T _reg cells and contain few immature CD4 ⁺CD25 ^-Foxp3 ^low T. cells. Interestingly, common γ chain (γc) knockout mice have been shown to have a near complete absence of Foxp3 ⁺ T _reg cells, including the immature CD25 ^-Foxp3 ^low subset. Therefore, other γc-cytokine(s) must be critically important during thymic development of CD4 ⁺CD25 ⁺Foxp3 ⁺ T _reg cells apart from the IL-2. The present study was undertaken to determine whether the γc-cytokines IL-7 or IL-15 normally contribute to expression of Foxp3 and Treg cell production. These studies revealed that mice double deficient in IL-2Rβ and 1L-7Rα contained a striking lack in the CD4 ⁺Foxp3 ⁺ population and the T _reg cell defect recapitulated the γc knockout mice. In the absence of IL-7R signaling, 1L-15/IL-15R interaction is dispensable for the production of CD4 ⁺CD25 ⁺Foxp3 ⁺ T _reg cells, indicating that normal thymic T _reg cell production likely depends on signaling through both IL-2 and IL-7 receptors. Selective thymic reconstitution of IL-2Rβ in mice double deficient in IL-2Rβ and IL-7Ra established that IL-2Rβ is dominant and sufficient to restore production of T _reg cells. Furthermore, the survival of peripheral CD4 ⁺Foxp3 ^low cells in IL-2R/β ^-/- mice appears to depend upon IL-7R signaling. Collectively, these data indicate that IL-7R signaling contributes to T _reg cell development and peripheral homeostasis.