Self-protection of cytotoxic lymphocytes: a soluble form of homologous restriction factor in cytoplasmic granules.
A soluble form of homologous restriction factor (HRF) has been isolated from the cytoplasmic granules of human large granular lymphocytes that were cultured in the presence of recombinant interleukin 2 for 2-3 weeks. The granule-derived protein (approximately 65 kDa) is soluble in detergent-free solution and reacts with antibody produced to membrane HRF. HRF was first described as a 65-kDa membrane protein of human erythrocytes capable of inhibiting the formation of transmembrane channels by the membrane attack complex of complement. It has also been isolated from activated human lymphocytes and shown to confer upon these cells relative resistance to lysis by the membrane attack complex and by the complement component C9-related protein of human cytotoxic lymphocytes. The soluble HRF of lymphocyte granules inhibits reactive lysis of erythrocytes by the membrane attack complex of human complement. It was also found to be a potent inhibitor of (i) the cytolytic activity of the C9-related protein of human cytotoxic lymphocytes, (ii) human large granular lymphocyte cytotoxicity, and (iii) the cytotoxic activity of human CD8+ lymphocytes obtained by cell sorting from recombinant interleukin 2-activated peripheral blood mononuclear cells. It is proposed that granule-derived soluble HRF and cell surface-membrane-bound HRF are involved in the mechanism of self-protection of killer lymphocytes.
Zalman
L S
LS
Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
Brothers
M A
MA
Müller-Eberhard
H J
HJ
D001798:Blood Proteins / Q000302:isolation & purification*; D018957:CD59 Antigens; D002352:Carrier Proteins; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D003594:Cytoplasmic Granules / Q000032:analysis*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008565:Membrane Proteins / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000032:analysis* / Q000187:drug effects; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; D018957:CD59 Antigens; D002352:Carrier Proteins; D007376:Interleukin-2; D008565:Membrane Proteins; D011994:Recombinant Proteins; C051590:CD59 protein, human; D003165:Complement System Proteins