Induction of expression of cell-surface homologous restriction factor upon anti-CD3 stimulation of human peripheral lymphocytes.

Abstract

Homologous restriction factor (HRF) is a 65-kDa membrane protein that inhibits transmembrane channel formation by the membrane-attack complex of complement and by the complement component C9-related cytolytic lymphocyte protein. Stimulation of resting peripheral human lymphocytes with the anti-CD3 monoclonal antibody OKT3 has been shown to induce cytotoxicity in the CD8+ subpopulation. As demonstrated here, OKT3 stimulation also induces expression of cell-surface HRF by CD4+ and CD8+ T lymphocytes. The small proportion of Leu 19+ natural killer lymphocytes present in peripheral blood mononuclear cells was found to express HRF prior to stimulation. Whereas unstimulated peripheral blood mononuclear cells were susceptible to lysis by the membrane-attack complex or by the C9-related protein, OKT3-stimulated peripheral blood mononuclear cells were relatively resistant to both the membrane-attack complex and C9-related protein. This acquired resistance was abrogated by blocking surface HRF with F(ab')2 anti-HRF, suggesting that resistance was due to lymphocyte-membrane HRF. By using solid-phase anti-HRF, a 65-kDa protein was isolated from the activated peripheral blood mononuclear cells and shown to be capable of conferring upon sheep erythrocytes the characteristic activity of human HRF.