CHIMERIC ANTI-CD4 MONOCLONAL-ANTIBODY CROSS-LINKED BY MONOCYTE FC-GAMMA RECEPTOR MEDIATES APOPTOSIS OF HUMAN CD4 LYMPHOCYTES

Previous studies have shown that murine anti-CD4 monoclonal antibody, cross-linked by rabbit anti-mouse immunoglobulin, could mediate apopto sis of murine CD4+ lymphocytes when they were stimulated by T cell rec eptor antibody In this study, we have shown that the murine anti-CD4 m onoclonal antibody, OKT4, can induce apoptosis in human CD4+ T cells s timulated 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 h uman, was able to cause apoptosis without cross-linking by a second an tibody. Similarly, abolition of PPD-induced proliferation of periphera l blood mononuclear cells by cM-T412 did not require cross-linking wit h rabbit anti-human immunoglobulin. Inhibition of proliferation by cM- T412 could be reduced by pre-treating monocytes with heat-aggregated h uman IgG. This suggested that monocyte Fcgamma receptors might be cros s-linking the human Fc of cM-T412. Propidium iodide staining together with immunofluorescence showed that the apoptotic cells were indeed CD 4+ lymphocytes. It is proposed that during treatment with cM-T412 in a utoimmune disease such as rheumatoid arthritis, cM-T412-coated CD4 T c ells, when they are subsequently stimulated by the unknown arthritogen ic antigen, may undergo apoptotic cell death through cross-linking of cM-T412 on Fcgamma receptor-positive cells within the joint.