title: Stat5 gene dosage in T cells modulates CD8+ T-cell homeostasis and attenuates contact hypersensitivity response in mice.
abstract: BACKGROUND
  Contact hypersensitivity assay (CHS) faithfully models human allergies. The Stat5 transcription factors are essential for both lymphocyte development and acute immune responses. Although consequences of Stat5 ablation and transgenic overexpression for the lymphocyte development and functions have been extensively studied, the role of Stat5 gene dosage in contact allergies has not been addressed.
  
  
  OBJECTIVE
  We investigated the effect of Stat5 gene dosage modulation in contact allergies using CHS in mice.
  
  
  METHODS
  Transgenic animals heterozygous for the germline Stat5 null allele were subjected to CHS. To dissect cell type sensitive to Stat5 gene dosage, animals with Stat5 haplo-insufficiency in T cells, where one Stat5 allele was removed by Lck-Cre-mediated deletion (Stat5(ΔT/+)), were tested by CHS. Frequency of T cells, B cells, and monocytes were analyzed in Stat5(ΔT/+) and wild-type animals by flow cytometry. Proliferation of Stat5(ΔT/+) CD8(+) T cells was studied in vitro by stimulation with IL-4 and IL-2 cytokines, and changes in the expression of Stat5 target genes were assayed by quantitative real-time PCR assay.
  
  
  RESULTS
  Haplo-insufficiency of Stat5 in T cells leads to the reduction in CD8(+) T cells in all lymphoid organs and attenuates CHS response. Stat5(ΔT/+) CD8(+) T cells failed to fully activate Stat5-dependent expression of cell cycle/survival target genes, such as Bcl2 and Pim1, and to proliferate efficiently in response to IL-2 and IL-4 cytokine.
  
  
  CONCLUSIONS
  Our data identify Stat5 as a dose-dependent regulator of CD8(+) T-cell functions in contact allergies and suggest that modulation of Stat5 dosage could be used to target contact allergies in humans.
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Nivarthi
authors.forename: M
authors.initials: M
authors.lastname: Prchal-Murphy
authors.forename: A
authors.initials: A
authors.lastname: Swoboda
authors.forename: M
authors.initials: M
authors.lastname: Hager
authors.forename: M
authors.initials: M
authors.lastname: Schlederer
authors.forename: L
authors.initials: L
authors.lastname: Kenner
authors.forename: J
authors.initials: J
authors.lastname: Tuckermann
authors.forename: V
authors.initials: V
authors.lastname: Sexl
authors.forename: R
authors.initials: R
authors.lastname: Moriggl
authors.forename: O
authors.initials: O
authors.lastname: Ermakova
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D018628:Gene Dosage; D005854:Germ Cells / Q000378:metabolism; D057895:Haploinsufficiency; D006706:Homeostasis; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D050799:STAT5 Transcription Factor / Q000235:genetics*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: D050799:STAT5 Transcription Factor
keywords: Stat5; T cells; allergic contact dermatitis