CD8⁺ T cells lyse autologous monocytes in the presence of anti-CD3 monoclonal antibody: Association with interleukin-1 production

Human peripheral blood T cells lysed autologous or allogeneic monocytes, but not polymorphonuclear cells (PMN) or lymphocytes, in the presence of anti-CD3 (OKT3 (IgG_2a) or anti-Leu 4 (IgG₁)) monoclonal antibody (mAb). Other mAbs such as OKT4 (IgG_2b), OKT8 (IgG_2a), OKT11 (IgG_2a), and OKM1 (IgG_2a) did not mediate lysis of monocytes. Lysis of monocytes also did not occur in the presence of F(ab′)₂ fragments of OKT3 mAb. OKT3 mAb and control murine IgG_2a mAb, but not F(ab′)₂ fragments of OKT3 mAb, were bound to the monocyte cell surface. Purified human IgG₁ and IgG₃ myeloma proteins, polyclonal human IgG, or Con A inhibited anti-CD3-dependent T-cell cytotoxicity against monocytes when added to the 4-hr ⁵¹Cr-release assay. Pretreatment of monocytes with an irrelevant murine IgG_2a mAb also inhibited OKT3 mAb (IgG_2a)-dependent lysis of these cells, but did not affect anti-Leu 4 mAb (IgG₁)-dependent lysis, suggesting that two different Fc receptors were involved. These results strongly suggest that Fc IgG receptors on monocytes are a critical structure for anti-CD3-dependent cytotoxicity. Lysis of monocytes was accompanied by interleukin-1 (IL-1) production, which was detected in supernatants from 4-hr cultures of T cells and monocytes in the presence of the OKT3 mAb. Both anti-CD3-dependent lysis of monocytes and IL-1 production were severely decreased after treatment of T cells with either OKT3 or OKT8 mAb plus complement, but were not affected significantly by treatment with the OKT4 mAb plus complement. Purified CD8⁺ cells, prepared using the cell sorter, exhibited significant levels of anti-CD3-dependent monocyte lysis (>10%). In contrast, purified CD4⁺ cells did not exhibit significant levels of anti-CD3-dependent cytotoxicity (<10%). Production of high concentrations of IL-1 was observed in cultures of purified CD8⁺ cells and monocytes in the presence of anti-CD3 mAb. Only low concentrations of IL-1 were detected in cultures of purified CD4⁺ cells, monocytes, and OKT3 mAb. These results suggest that CD8⁺ cells are primarily responsible for lysis of monocytes, which is associated with IL-1 production. It appears that anti-CD3 mAb brings CD8⁺ T cells and monocytes into close proximity by binding to the CD3 antigen on T cells and to the Fc IgG receptor on monocytes. This interaction results in lysis of monocytes primarily by CD8⁺ cells, after bypassing any antigen recognition requirements that may be otherwise needed. Lysis of monocytes appears to be associated with IL-1 release.