IL-2 Regulates CD103 Expression on CD4+ T Cells in Scurfy Mice that Display Both CD103-Dependent and Independent Inflammation

Abstract

Scurfy (Sf) mice lack CD4+Foxp3+ regulatory T cells and develop fatal multiorgan inflammation (MOI) mediated by CD4+ T cells. Introducing Il2−/− gene into Sf mice (Sf.Il2−/−) inhibited inflammation in skin and lung. As a major integrin receptor for the organs, we compared CD103 expression on the CD4+ T cells of B6, Il2−/−, Sf, and Sf.Il2−/− mice. CD103+CD4+ T cells, but not CD8+ T cells or CD11c+ dendritic cells, were significantly up-regulated only in Sf mice, indicating Il2−/− dominantly and specifically inhibited CD103 up-regulation in Sf CD4+ T cells. In addition, CD4+Foxp3+ regulatory T cell CD103 expression was not reduced in Il2−/− mice. Introducing CD103−/− into Sf mice inhibited inflammation in skin and lung as compared with age-matched Sf mice, but they died at ∼7 wk old with inflammation developed in skin, lungs, and colon, demonstrating fatal MOI induced by CD103-independent mechanism. Transfer of Sf CD4+ T cells induced MOI more rapidly than CD103−CD4+ T cells, indicating the presence of CD103-dependent mechanism for inflammation. In vitro stimulation with anti-CD3 plus anti-CD28 beads confirmed that CD103 induction in the CD4+Foxp3− T cells in Il2−/− and Sf.Il2−/− is defective and cannot be restored by rIL-2 or rIL-15. The data indicate that IL-2 is required for optimal CD103 induction on CD4+ T cells in Sf mice and this effect contributes to inflammation in an organ-specific manner. IL-2 also has additional roles because the protection of skin and lung inflammation in Sf.Il2−/−, but not Sf.CD103−/− mice is lifelong and Sf.Il2−/− mice have longer lifespan than Sf.CD103−/− mice.