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

Abstract

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 (IgG 1)) 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 IgG 1 and IgG 3 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 (IgG 1)-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.