Summary auto-generated
This study examined cytolytic immune cells that kill pseudorabies virus (PRV)-infected cells in pigs. Peripheral blood mononuclear cells from PRV-immune pigs were stimulated in vitro with live PRV and tested for their ability to lyse infected target cells. The researchers found that the primary cytolytic effector cells displayed characteristics of natural killer (NK) or lymphokine-activated killer (LAK) cells rather than classical major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTLs). Evidence supporting this included: cytolysis was not MHC-restricted, it was mediated by CD2+CD4-CD8 dim/negative cells, it occurred even when stimulated with UV-inactivated virus, and effector cells also lysed the NK-susceptible K562 cell line. Target cells transfected with PRV glycoproteins gB or gC were lysed as efficiently as virus-infected cells, whereas cells expressing gD or immediate-early proteins were not. These findings suggest that NK/LAK cells, rather than classical CTLs, may play a primary role in porcine immunity to PRV, though the biological significance of these cells in vivo remains to be determined.
Key findings
- Cytolytic effector cells generated from PRV-immune pigs display characteristics of NK/LAK cells rather than classical MHC-restricted CTLs
- Cytolysis was non-MHC-restricted, mediated by CD2+CD4-CD8 dim/negative cells, and occurred with both live and UV-inactivated virus
- PRV glycoproteins gB and gC on transfected cells were efficiently lysed by effector cells, similar to virus-infected cells
- NK/LAK cell activity was selectively induced by viral antigen stimulation in immune animals but not in non-immune controls
- IL-2 stimulation alone could generate LAK cells capable of lysing PRV-infected cells and K562 targets in both immune and non-immune animals
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Abstract
We examined cytolytic cells that lyse pseudorabies virus (PRV)-infected cells in pigs. In vitro stimulation of peripheral blood mononuclear cells from PRV-immune pigs with live PRV generated cells that lysed PRV-infected immortalized B cells. Several lines of evidence indicated a major contribution of non-major histocompatibility complex (MHC)-restricted cytolytic cells, which displayed characteristics of natural killer (NK) or lymphokine-activated killer cells: cytolysis was non-MHC-restricted, depended on CD2+CD4-CD8bright- (or CD2+CD4-CD8dull+) cells, was strongly augmented by in vitro antigenic stimulation and was not limited to virus-infected cells, i.e. the NK cell-susceptible target cell line K562 was also lysed. Cytolytic cells were also generated by in vitro antigenic stimulation with UV-inactivated PRV. Target cells transfected with and stably expressing PRV gB or gC were lysed to the same degree as PRV-infected target cells.
* Author for correspondence. Present address: Research Laboratory for Infectious Diseases, RIVM, PO Box 1, 3720 BA Bilthoven, The Netherlands. Fax +31 30 2744449. e-mail TG.Kimman@RIVM.NL