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-γ, 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.
authors: Department of Microbiology and Immunology, Loyola University Chicago, 2160 South First Ave., Maywood, IL 60153, USA.
authors: Mutsumi
authors: M
authors: Yamamoto
authors: Yoichi
authors: Y
authors: Seki
authors: Kazuyuki
authors: K
authors: Iwai
authors: Iei
authors: I
authors: Ko
authors: Alicia
authors: A
authors: Martin
authors: Noriko
authors: N
authors: Tsuji
authors: Shuji
authors: S
authors: Miyagawa
authors: Robert B
authors: RB
authors: Love
authors: Makio
authors: M
authors: Iwashima
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D055879:Gene Knock-In Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006262:Health; D059765:Homologous Recombination / Q000235:genetics; D019426:Integrases / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
chemical_list: D000954:Antigens, Surface; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases