title: Differential requirements for IRF-2 in generation of CD1d-independent T cells bearing NK cell receptors.
abstract: NK cell receptors (NKRs) such as NK1.1, NKG2D, and Ly49s are expressed on subsets of CD1d-independent memory phenotype CD8(+) and CD4(-)CD8(-) T cells. However, the mechanism for the generation and functions of these NKR(+) T cells remained elusive. In this study, we found that CD1d-independent Ly49(+) T cells were reduced severely in the spleen, bone marrow, and liver, but not thymus, in mice doubly deficient for IFN regulatory factor-2 (IRF-2) and CD1d, in which the overall memory phenotype T cell population was contrastingly enlarged. Because a large fraction of Ly49(+) T cells coexpressed NK1.1 or NKG2D, the reduction of Ly49(+) T cells resulted indirectly in underrepresentation of NK1.1(+) or NKG2D(+) cells. Ly49(+) T cell deficiency was observed in IRF-2(-/-) mice additionally lacking IFN-α/βR α-chain (IFNAR1) as severely as in IRF-2(-/-) mice, arguing against the involvement of the accelerated IFN-α/β signals due to IRF-2 deficiency. Rather, mice lacking IFN-α/βR alone also exhibited relatively milder Ly49(+) T cell reduction, and IL-2 could expand Ly49(+) T cells from IFNAR1(-/-), but not from IRF-2(-/-), spleen cells in vitro. These results together indicated that IRF-2 acted in Ly49(+) T cell development in a manner distinct from that of IFN-α/β signals. The influence of IRF-2 deficiency on Ly49(+) memory phenotype T cells observed in this study suggested a unique transcriptional program for this T cell population among other NKR(+) T and memory phenotype T cells.
authors.affiliation: Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Notake
authors.forename: Shin
authors.initials: S
authors.lastname: Horisawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Sanjo
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Hida
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Taki
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping / Q000379:methods; D050836:Interferon Regulatory Factor-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D055607:Receptors, Natural Killer Cell / Q000378:metabolism*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D050836:Interferon Regulatory Factor-2; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055607:Receptors, Natural Killer Cell