title: Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation.
abstract: To determine the tissue-specific functions of SOCS-1, mice were generated in which the SOCS-1 gene could be deleted in individual tissues. A reporter gene of SOCS-1 promoter activity was also inserted. Using the reporter, high SOCS-1 expression was found at the CD4(+)CD8(+) stage in thymocyte development. To investigate the function of this expression, the SOCS-1 gene was specifically deleted throughout the thymocyte/T/NKT cell compartment. Unlike SOCS-1(-/-) mice, these mice did not develop lethal multiorgan inflammation but developed multiple lymphoid abnormalities, including enhanced differentiation of thymocytes toward CD8(+) T cells and very high percentages of peripheral CD8(+) T cells with a memory phenotype (CD44(hi)CD25(lo)CD69(lo)). These phenotypes were found to correlate with hypersensitivity to the gamma-common family of cytokines.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Mark M W
authors.initials: MM
authors.lastname: Chong
authors.forename: Ann L
authors.initials: AL
authors.lastname: Cornish
authors.forename: Rima
authors.initials: R
authors.lastname: Darwiche
authors.forename: Edouard G
authors.initials: EG
authors.lastname: Stanley
authors.forename: Jared F
authors.initials: JF
authors.lastname: Purton
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Hilton
authors.forename: Robyn
authors.initials: R
authors.lastname: Starr
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
authors.forename: Thomas W H
authors.initials: TW
authors.lastname: Kay
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D007156:Immunologic Memory; D016130:Immunophenotyping; D019426:Integrases / Q000235:genetics; D015851:Interleukin-7 / Q000494:pharmacology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014764:Viral Proteins / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D015851:Interleukin-7; D012333:RNA, Messenger; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014764:Viral Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C045073:Cre recombinase; D019426:Integrases