TY - JOUR
T1 - CD8+ T cells lyse autologous monocytes in the presence of anti-CD3 monoclonal antibody
T2 - Association with interleukin-1 production
AU - Itoh, Kyogo
AU - Balch, Charles M.
AU - Trial, Joann
AU - Platsoucas, Chris D.
N1 - Funding Information:
’ This work was supported in part by Grants CA-27 197, CA-131 48, CA-030 13, and CA-4 1699 from the National Institutes of Health, Grants IM-409D and CH-420 from the American Cancer Society, by a grant from the Eleanor Naylor Dana Charitable Trust, and by a grant from the Erwin Zaban Melanoma Research Fund.
PY - 1988/7
Y1 - 1988/7
N2 - Human peripheral blood T cells lysed autologous or allogeneic monocytes, but not polymorphonuclear cells (PMN) or lymphocytes, in the presence of anti-CD3 (OKT3 (IgG2a) or anti-Leu 4 (IgG1)) monoclonal antibody (mAb). Other mAbs such as OKT4 (IgG2b), OKT8 (IgG2a), OKT11 (IgG2a), and OKM1 (IgG2a) 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 IgG2a 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 IgG2a mAb also inhibited OKT3 mAb (IgG2a)-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.
AB - Human peripheral blood T cells lysed autologous or allogeneic monocytes, but not polymorphonuclear cells (PMN) or lymphocytes, in the presence of anti-CD3 (OKT3 (IgG2a) or anti-Leu 4 (IgG1)) monoclonal antibody (mAb). Other mAbs such as OKT4 (IgG2b), OKT8 (IgG2a), OKT11 (IgG2a), and OKM1 (IgG2a) 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 IgG2a 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 IgG2a mAb also inhibited OKT3 mAb (IgG2a)-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.
UR - http://www.scopus.com/inward/record.url?scp=0023809437&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023809437&partnerID=8YFLogxK
U2 - 10.1016/0008-8749(88)90320-6
DO - 10.1016/0008-8749(88)90320-6
M3 - Article
C2 - 3260540
AN - SCOPUS:0023809437
SN - 0008-8749
VL - 114
SP - 257
EP - 271
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -