title: IL-15 trans-presentation regulates homeostasis of CD4(+) T lymphocytes.
abstract: Interleukin-15 (IL-15) is essential for the survival of memory CD8(+) and CD4(+) T cell subsets, and natural killer and natural killer T cells. Here, we describe a hitherto unreported role of IL-15 in regulating homoeostasis of naive CD4(+) T cells. Adoptive transfer of splenocytes from non-obese diabetic (NOD) mice results in increased homeostatic expansion of T cells in lymphopenic NOD.scid.Il15(-/-) mice when compared to NOD.scid recipients. The increased accumulation of CD4(+) T cells is also observed in NOD.Il15(-/-) mice, indicating that IL-15-dependent regulation also occurs in the absence of lymphopenia. NOD.scid mice lacking the IL-15Rα chain, but not those lacking the common gamma chain, also show increased accumulation of CD4(+) T cells. These findings indicate that the IL-15-mediated regulation occurs directly on CD4(+) T cells and requires trans-presentation of IL-15. CD4(+) T cells expanding in the absence of IL-15 signaling do not acquire the characteristics of classical regulatory T cells. Rather, CD4(+) T cells expanding in the absence of IL-15 show impaired antigen-induced activation and IFN-γ production. Based on these findings, we propose that the IL-15-dependent regulation of the naive CD4(+) T-cell compartment may represent an additional layer of control to thwart potentially autoreactive cells that escape central tolerance, while permitting the expansion of memory T cells.
authors.affiliation: Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Qué., Canada.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Qué., Canada.
authors.forename: Diwakar
authors.initials: D
authors.lastname: Bobbala
authors.affiliation: Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Qué., Canada.
authors.forename: Yuneivy
authors.initials: Y
authors.lastname: Cepero Donates
authors.affiliation: Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Qué., Canada.
authors.forename: Marian
authors.initials: M
authors.lastname: Mayhue
authors.affiliation: 1] Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Qué., Canada [2] Centre de recherche clinique Etienne-Le Bel, Sherbrooke, QC, Canada.
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.affiliation: 1] Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Qué., Canada [2] Centre de recherche clinique Etienne-Le Bel, Sherbrooke, QC, Canada.
authors.forename: Sheela
authors.initials: S
authors.lastname: Ramanathan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D006706:Homeostasis; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D053720:Interleukin-15 Receptor alpha Subunit / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D007371:Interferon-gamma