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. [Copyright &y& Elsevier]