title: Differential induction of IL-17, IL-10, and IL-9 in human T helper cells by B7h and B7.1.
abstract: ICOS and CD28 are expressed by T cells and are involved in costimulation of cytokine production in T helper (TH) cells. ICOS binds B7h expressed by several cell types, whereas CD28 binds B7.1 and B7.2 expressed by activated antigen presenting cells. This work investigated the role of B7h and B7.1 in TH17 and TH9 cell differentiation by assessing activity of recombinant B7h-Fc and B7.1-Fc on human naïve TH cells activated in the presence of different combinations of exogenous cytokines. In the presence of TGF-β1 and IL-1β (TH17 promoting condition), B7h-Fc was more effective than B7.1-Fc in inducing IL-17A and IL-10 secretion, whereas B7.1-Fc was more effective in inducing IL-17F. Dual costimulation with B7h-Fc and B7.1-Fc displayed an intermediate pattern with predominance of IL-17F over IL-17A, secretion of high levels of IL-10, and secretion of IL-9 levels lower than those induced by B7.1-Fc alone. In the presence of TGF-β1 and IL-4 (TH9 promoting condition), B7h-Fc induced IL-17A only, whereas B7.1-Fc induced also IL-17F, IL-10, and high levels of IL-9. Experiments on memory TH cells showed that B7h-Fc mainly supported secretion of IL-17A and IL-10, whereas B7.1-Fc supported secretion of IL-17A, IL-17F, IL-10, and IL-9. These data indicate that B7h and B7.1 play different roles in modulation of TH17 and TH9 differentiation. This plasticity might be important in the immune response to pathogens and tumors, and in the development of autoimmune diseases, and should be taken in consideration in designing of immunotherapeutic protocols triggering ICOS or CD28.
authors.affiliation: Interdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Health Sciences, "A. Avogadro" University of Eastern Piedmont, 28100 Novara, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Mesturini
authors.forename: Casimiro L
authors.initials: CL
authors.lastname: Gigliotti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orilieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cappellano
authors.forename: Maria F
authors.initials: MF
authors.lastname: Soluri
authors.forename: Elena
authors.initials: E
authors.lastname: Boggio
authors.forename: Abiy
authors.initials: A
authors.lastname: Woldetsadik
authors.forename: Chiara
authors.initials: C
authors.lastname: Dianzani
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: Junji
authors.initials: J
authors.lastname: Yagi
authors.forename: Josè M
authors.initials: JM
authors.lastname: Rojo
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D018122:B7-1 Antigen / Q000494:pharmacology*; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000494:pharmacology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000378:metabolism; D016906:Interleukin-9 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D018106:CD28 Antigens; C556692:ICOS protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D020381:Interleukin-17; D053583:Interleukin-1beta; D016906:Interleukin-9; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10
keywords: APC; CD28 IL-17; ICOS; IL-; IL-9; INF-γ; Ig; PB; PBMC; T cell receptor; T helper; TCR; TGF-β; TH; TH17; TH9; antigen-presenting cells; immunoglobulin; inducible costimulator; interferon-γ; interleukine-; mAbs; monoclonal antibody; peripheral blood; peripheral blood mononuclear cells; transforming growth factor-β