Lysis of uninfected and virus-infected cells in vivo: a rejection mechanism in addition to that mediated by natural killer cells.
To examine the lysis of virus-infected cells in vivo, uninfected and lymphocytic choriomeningitis virus (LCMV)-infected L-929 cells were labeled in vitro with [125I]-iododeoxyuridine and implanted intravenously into mice. Natural cytotoxicity against both uninfected and virus-infected cells was demonstrated in normal uninfected mice, but LCMV-infected cells were cleared from the lungs and whole bodies more rapidly than uninfected cells. Treatment of L-929 cells with defective interfering LCMV inhibited standard virus synthesis and protected the target cells from enhanced in vivo rejection. The in vivo rejection was apparently mediated by a cellular constituent of the host immune response and not simply a result of virus-induced cytopathic effects on the target cell, as hydrocortisone acetate and cyclophosphamide each reduced rejection of both target cell types and eliminated the enhanced rejection of LCMV-infected cells. The enhanced rejection of LCMV-infected cells was not restricted by histocompatibility antigens, indicating that classic T-cell recognition was not involved in the lysis, and since the enhanced rejection of LCMV-infected cells was mediated by mice treated with cobra venom factor, complement was also not involved in the lysis. Although moderate levels of interferon (102 U/ml) were present in the sera and although there was a modest activation of natural killer (NK) cells in the lungs of LCMV-infected cell recipients but not uninfected cell recipients, the enhanced rejection of virus-infected cells did not appear to be NK cell mediated. Normal mice and mice depleted of NK cell activity by in vivo treatment with antibody to asialo ganglio-n-tetraosylceramide ( AGM1 ) rejected uninfected and LCMV-infected L-929 cells similarly. This antibody markedly inhibited the rejection of NK-sensitive YAC-1 cells. In addition to the natural cytotoxicity directed against virus-infected cells, a second nonspecific rejection mechanism appeared in response to treatment protocols which induced interferon. Polyinosinic-polycytidylic acid and infection with LCMV augmented in vivo rejection of both uninfected and LCMV-infected L-929 cells but eliminated the differential rejection of the virus-infected cells. Infection with LCMV also augmented the in vivo rejection of the NK-sensitive target cell, YAC-1. In vivo treatments with anti- AGM1 sera only moderately inhibited the elevated rejection of uninfected and LCMV-infected L-929 cells, indicating that the enhanced rejection of these target cells was predominantly mediated by a mechanism other than that mediated by NK cells.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D002460:Cell Line; D003165:Complement System Proteins / Q000032:analysis; D003520:Cyclophosphamide / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007739:L Cells / Q000276:immunology; D007942:Leukemia, Experimental; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains
C021650:hydrocortisone acetate; D003520:Cyclophosphamide; D003165:Complement System Proteins; D006854:Hydrocortisone