title: Modulating T cell functions does not alleviate chronic inflammatory skin lesions in K5.TGF beta 1 transgenic mice.
abstract: To use mice with chronic hyperproliferative skin inflammation as psoriasis models, their thorough phenotypic and functional characterization is indispensable. Mice with keratin 5 promoter-controlled overexpression of latent human Transforming Growth Factor (TGF)beta1 within the basal epidermis (K5.TGF beta 1 mice) show a psoriasiform phenotype, but the underlying pathogenic mechanisms are not entirely clear. To elucidate the contribution of T lymphocytes to the pathogenesis in K5.TGF beta 1 mice, we used three complementary approaches: first, peripheral T cells were eradicated via systemic treatment with CD3- or CD4-depleting antibodies. However, this elimination did not alleviate the chronic inflammatory disorder. Second, bone marrow transplantation from transgenic mice into wildtype recipients and vice versa resulted in the expected reconstitution of both adaptive and innate immune system but had little effect on the cutaneous phenotype both in wildtype and transgenic chimeras. Third, based on the hypothesis that the disease course could be modulated by regulatory T cells (Tregs), we expanded Tregs in vivo using a superagonistic anti-CD28 antibody. While this treatment achieved a threefold increase in Foxp3-expressing Tregs, there was little, if any, effect on the chronic skin inflammation. We conclude from our findings that T cells play little, if any, role in the skin lesions of K5.TGF beta 1 mice.
authors.affiliation: Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Michaelis
authors.forename: Katrin
authors.initials: K
authors.lastname: Wallbrecht
authors.forename: Andreas
authors.initials: A
authors.lastname: Kerstan
authors.forename: Niklas
authors.initials: N
authors.lastname: Beyersdorf
authors.forename: Cortny
authors.initials: C
authors.lastname: Williams
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerkau
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D016026:Bone Marrow Transplantation; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D053569:Keratin-15; D053555:Keratin-5 / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014916:Whole-Body Irradiation
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D053773:Transforming Growth Factor beta1