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

• Published in: The Journal of immunology (1950) Vol. 183; no. 2; pp. 1065 - 1073
• Main Authors: Sharma, Rahul, Sung, Sun-sang Joe, Abaya, Christian E, Ju, Angela Chiao-Ying, Fu, Shu Man, Ju, Shyr-Te
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2009
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - physiology; Cause of Death; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; Inflammation - etiology; Inflammation - mortality; Integrin alpha Chains - genetics; Integrin alpha Chains - physiology; Interleukin-2 - deficiency; Interleukin-2 - physiology; Longevity; Lung - pathology; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Skin - pathology; T-Lymphocytes, Regulatory; Transcriptional Activation
• DOI: 10.4049/jimmunol.0804354
• ISSN: 0022-1767

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 approximately 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.