Effect of rhTACI-Ig fusion protein on antigen-specific T cell responses from keyhole limpet haemocyanin challenged mice

Mol Immunol. 2011 Oct;49(1-2):380-6. doi: 10.1016/j.molimm.2011.09.007. Epub 2011 Oct 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / metabolism
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cell Separation
  • Flow Cytometry
  • Hemocyanins / immunology*
  • Humans
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / immunology*
  • Recombinant Fusion Proteins / metabolism
  • Spleen / cytology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism

Substances

  • B-Cell Activating Factor
  • Recombinant Fusion Proteins
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Hemocyanins
  • keyhole-limpet hemocyanin
  • TACI receptor-IgG Fc fragment fusion protein