title: Effect of rhTACI-Ig fusion protein on antigen-specific T cell responses from keyhole limpet haemocyanin challenged mice.
abstract: In addition to modulate B cells function, B cell activating factor belonged to TNF family (BAFF) also regulates T cells response via BAFFR and transmembrane activator and calcium modulator and cyclophilin-ligand interactor (TACI) expressing on activated T cells. This study explored the effect of a recombinant fusion protein containing the extracellular ligand-binding portion of TACI and the Fc portion of human immunoglobulin G (TACI-Ig) on activated T cells that were obtained from antigen-specific T-cell responses mice model induced by keyhole limpet haemocyanin (KLH), the characteristics of KLH-challenged mice were observed simultaneously. KLH immunization leaded to a significant positive relationship between BAFF level in serum and the extent of spleen histopathology. Serum concentration of BAFF, APRIL, IgM and IgG antibodies to KLH, and IL-4 were increased under KLH immunization, but IL-2 synthesis was decreased, resulting in a downregulation of IL-2/IL-4 ratio. Antigen-specific T cells proliferation, IL-5 production, the percentage of Th and activation T cells were significantly upregulated, however, IL-2 secretion and the percentage of naïve T cells were downregulated in vitro. RhBAFF co-stimulation further evoked T cells hyperplasy, IL-4 and IFN-γ expression, the subgroups of Th, early antigen activation and activation T cells were also further increased. On the contrary, naïve T cells were further reduced under rhBAFF stimuli. Administration of rhTACI-Ig significantly inhibited T cells proliferation, cytokines production and T cells differentiation, and the inhibitory effects might be associated with its ability to neutralize both the exogenous and endogenetic BAFF and APRIL.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry, Hefei 230032, Anhui Province, PR China.
authors.forename: Qing-Tong
authors.initials: QT
authors.lastname: Wang
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Ma
authors.forename: Bei
authors.initials: B
authors.lastname: Huang
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D005434:Flow Cytometry; D006433:Hemocyanins / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D011993:Recombinant Fusion Proteins; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; C524618:TACI receptor-IgG Fc fragment fusion protein