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Chimaeric anti‐CD4 monoclonal antibody cross‐linked by monocyte Fcγ receptor mediates apoptosis of human CD4 lymphocytes

1993; Wiley; Volume: 23; Issue: 10 Linguagem: Inglês

10.1002/eji.1830231043

1521-4141

Ernest Choy, James Adjaye, LESLEY A. FORREST, Gabrielle Kingsley, G S Panayi,

Immunotherapy and Immune Responses

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 Fcγ 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 Fey receptor‐positive cells within the joint.