title: Elimination of both CD4+ and CD8+ T cells but not B cells eliminates inflammation and prolongs the survival of TGFbeta1-deficient mice.
abstract: Transforming growth factor beta1 (TGFbeta1) is a potent negative immunoregulatory molecule. We have previously shown that the autoimmune-mediated weaning-age lethality of Tgfb1-/- mice is reversed upon genetic combination with Scid or Rag null alleles. Here, we show that elimination of T but not B cells is sufficient for the reversal, but elimination of either CD4+ or CD8+ cells is not. Although elimination of B cells does not rescue TGFbeta1-deficient animals from autoimmunity, B cells are hyperresponsive to LPS in the absence of TGFbeta1. TGFbeta1 deficiency leads to activation of CD8+ T cells as suggested by down-modulation of CD8 even in the absence of CD4+ T cells. This study provides evidence that both CD4+ and CD8+ T cells, but not B cells, have the ability to cause inflammation in the absence of TGFbeta1. However, though TGFbeta1-deficient B cells are hyperresponsive to stimulation, alone they are not sufficient to cause inflammation.
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Ramireddy
authors.initials: R
authors.lastname: Bommireddy
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Engle
authors.forename: Ilona
authors.initials: I
authors.lastname: Ormsby
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Boivin
authors.forename: George F
authors.initials: GF
authors.lastname: Babcock
authors.forename: Thomas
authors.initials: T
authors.lastname: Doetschman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D010641:Phenotype; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D053773:Transforming Growth Factor beta1
chemical_list: C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1