Chimaeric anti-CD4 monoclonal antibody cross-linked by monocyte Fc gamma receptor mediates apoptosis of human CD4 lymphocytes

Eur J Immunol. 1993 Oct;23(10):2676-81. doi: 10.1002/eji.1830231043.

Abstract

Previous studies have shown that murine anti-CD4 monoclonal antibody, cross-linked by rabbit anti-mouse immunoglobulin, could mediate apoptosis of murine CD4+ lymphocytes when they were stimulated by T cell receptor antibody. In this study, we have shown that the murine anti-CD4 monoclonal antibody, OKT4, can induce apoptosis in human CD4+ T cells stimulated by the recall antigen tuberculin purified protein derivative (PPD) only when cross-linked by rabbit anti-mouse immunoglobulin. The chimeric anti-CD4 monoclonal antibody, cM-T412 whose Fc fragment is human, was able to cause apoptosis without cross-linking by a second antibody. Similarly, abolition of PPD-induced proliferation of peripheral blood mononuclear cells by cM-T412 did not require cross-linking with rabbit anti-human immunoglobulin. Inhibition of proliferation by cM-T412 could be reduced by pre-treating monocytes with heat-aggregated human IgG. This suggested that monocyte Fc gamma receptors might be cross-linking the human Fc of cM-T412. Propidium iodide staining together with immunofluorescence showed that the apoptotic cells were indeed CD4+ lymphocytes. It is proposed that during treatment with cM-T412 in autoimmune disease such as rheumatoid arthritis, cM-T412-coated CD4 T cells, when they are subsequently stimulated by the unknown arthritogenic antigen, may undergo apoptotic cell death through cross-linking of cM-T412 on Fc gamma receptor-positive cells within the joint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Apoptosis / immunology*
  • CD4 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cross-Linking Reagents
  • DNA / metabolism
  • Humans
  • Lymphocyte Activation
  • Mice
  • Receptors, IgG / metabolism*
  • Recombinant Fusion Proteins / immunology
  • Tuberculin / immunology

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • Cross-Linking Reagents
  • Receptors, IgG
  • Recombinant Fusion Proteins
  • Tuberculin
  • DNA