Ontogeny and localization of the cells produce IL-2 in healthy animals Journal Article

Authors: Yamamoto, M.; Seki, Y; Iwai, K; Ko, I.; Martin, A.; Tsuji, N.; Miyagawa, S.; Love, R. B.; Iwashima, M
Article Title: Ontogeny and localization of the cells produce IL-2 in healthy animals
Abstract: IL-2 is a growth factor for activated T cells and is required for maintenance of naturally arising regulatory T cells (nTregs). Mice defective in IL-2/IL-2 receptor signaling pathways have impaired nTregs and suffer from lymphoproliferative disorders, suggesting that IL-2 is present and functional in healthy animals. However, the cellular source of IL-2 is currently unknown. To determine which cells produce IL-2 in healthy animals, we established mice carrying cre gene knock in at the il-2 locus (termed IL-2(cre)). When IL-2(cre) mice were crossed with EGFP reporter mice, EGFP was exclusively expressed by a fraction of CD4 T cells present in both lymphoid and non-lymphoid tissues. Live imaging of IL-2(cre) mice that carry the luciferase reporter showed concentrated localization of luciferase(+) cells in Peyer's patches. These cells were not observed in new born mice but appeared within 3days after birth. Reduction of antigen receptor repertoire by transgene expression reduced their number, indicating that recognition of environmental antigens is necessary for generation of these IL-2 producers in healthy animals. A substantial fraction of EGFP(+) cells also produce IL-10 and IFN-gamma, a characteristic profile of type 1 regulatory T cells (Tr1). The data suggest that a group of Tr1 cells have addition roles in immune homeostasis by producing IL-2 along with other cytokines and help maintaining Tregs.
Journal Title: Cytokine
Volume: 61
Issue: 3
ISSN: 1096-0023; 1043-4666
Publisher: Unknown  
Journal Place: United States
Date Published: 2013
Start Page: 831
End Page: 841
Language: eng
Notes: ID: 13075; CI: Copyright (c) 2012; GR: R01 AI047266/AI/NIAID NIH HHS/United States; GR: R01 AI055022/AI/NIAID NIH HHS/United States; JID: 9005353; NIHMS437600; OID: NLM: NIHMS437600 [Available on 03/01/14]; OID: NLM: PMC3595346 [Available on 03/01/14]; PMCR: 2014/03/01 00:00; 2012/06/25 [received]; 2012/11/15 [revised]; 2012/11/27 [accepted]; 2013/01/16 [aheadofprint]; ppublish