Natural killer-mediated lysis of some but not all HSV-1- or VSV-infected targets requires the participation of HLA-DR-positive accessory cells.
Natural killer (NK)-mediated lysis of herpes simplex virus type 1-infected fibroblasts (HSV-FS) has been previously shown to require the co-operation of CD16-positive NK cells and an HLA-DR-positive accessory cell population. In contrast, lysis of K562 tumour cells requires the presence of only the Leu-11-positive cells. In the current study, targets of different morphologies, both virally infected and non-infected, were tested in an attempt to dissect out which target characteristics determine the need for accessory cell participation for NK-mediated lysis. Effector populations were obtained through antibody plus complement (C) depletions of subpopulations of human peripheral blood mononuclear cells using anti-HLA-DR+C (accessory cell depleted) or anti-CD16+C (NK depleted). The subpopulations were tested both alone and mixed together for their ability to mediate target lysis. Although NK-mediated lysis of most HSV-infected targets required the presence of HLA-DR-positive accessory cells, there was one set of exceptions. Lysis of the non-adherent Epstein-Barr virus (EBV)-transformed lymphoblastoid lines HSV-Raji, HSV-ARH and HSV-CCRF demonstrated only partial accessory cell dependence. All infected adherent cell lines were accessory cell dependent. In contrast, none of the adherent or non-adherent non-infected targets tested required the presence of DR-positive accessory cells for killing. Therefore, the presence of virus was an indicator of accessory cell dependence for NK-mediated kill except in the cases where HSV-infected EBV-transformed targets were used. Assay times of 4 hr versus 14 hr were conducted to determine if the kinetics of kill of various targets correlated with the requirement for accessory cells. A substantial percentage of the total lysis seen at 14 hr occurred within 4 hr for accessory cell independent lysis of the non-infected targets. In contrast, accessory cell-dependent kill of infected targets usually required longer incubation time for substantial lysis to occur, and correlated with interferon (IFN) production. NK-mediated lysis of vesicular stomatitis virus-infected fibroblasts required the presence of both the CD16- and HLA-DR-positive subpopulations, extending the role of DR-positive cells in NK-mediated killing beyond herpes virally infected targets.
Howell
D M
DM
Department of Pathology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.
Fitzgerald-Bocarsly
P
P
D000938:Antigen-Presenting Cells / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis*; D006561:Herpes Simplex / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus; D014777:Virus Diseases / Q000276:immunology*
D006684:HLA-DR Antigens; D007370:Interferon Type I