Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation.
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.
Chong
Mark M W
MM
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Cornish
Ann L
AL
Darwiche
Rima
R
Stanley
Edouard G
EG
Purton
Jared F
JF
Godfrey
Dale I
DI
Hilton
Douglas J
DJ
Starr
Robyn
R
Alexander
Warren S
WS
Kay
Thomas W H
TW
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
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