title: Shb deficient mice display an augmented TH2 response in peripheral CD4+ T cells.
abstract: BACKGROUND
  Shb, a ubiquitously expressed Src homology 2 domain-containing adaptor protein has previously been implicated in the signaling of various tyrosine kinase receptors including the TCR. Shb associates with SLP76, LAT and Vav, all important components in the signaling cascade governing T cell function and development. A Shb knockout mouse was recently generated and the aim of the current study was to address the importance of Shb deficiency on T cell development and function.
  
  
  RESULTS
  Shb knockout mice did not display any major changes in thymocyte development despite an aberrant TCR signaling pattern, including increased basal activation and reduced stimulation-induced phosphorylation. The loss of Shb expression did however affect peripheral CD4+ T(H) cells resulting in an increased proliferative response to TCR stimulation and an elevated IL-4 production of naïve T(H) cells. This suggests a T(H)2 skewing of the Shb knockout immune system, seemingly caused by an altered TCR signaling pattern.
  
  
  CONCLUSIONS
  Our results indicate that Shb appears to play an important modulating role on TCR signaling, thus regulating the peripheral CD4+ T(H)2 cell response.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Gustafsson
authors.forename: Gabriela
authors.initials: G
authors.lastname: Calounova
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hjelm
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Kriz
authors.forename: Birgitta
authors.initials: B
authors.lastname: Heyman
authors.forename: Kjell-Olov
authors.initials: KO
authors.lastname: Grönvik
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mostoslavsky
authors.forename: Michael
authors.initials: M
authors.lastname: Welsh
mesh_terms: D000483:Alleles; D000818:Animals; D001772:Blood Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
chemical_list: D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; C085634:Shb protein, mouse