Cytotoxic Macrophages Induced in Hamsters by Vaccinia Virus: Selective Cytotoxicity for Virus-Infected Targets by Macrophages Collected Late After Immunization

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Abstract
Peritoneal macrophages from LHC/Lak hamsters infected with vaccinia virus were tested for cytotoxicity against uninfected and vaccinia or herpes simplex virus-infected semiallogeneic target cells (BHK and PARA-7) in a 51Cr cytotoxicity assay. Macrophages were tested between 3 and 34 days after immunization of hamsters with 1 × 107 PFU of vaccinia virus. Peak cytotoxicity against BHK infected with vaccinia virus (BHKV) or herpes simplex virus (BHKH) occurred at 5 days after immunization and declined to baseline by 34 days. At no time after immunization was there evidence of preferential killing of the specific BHKV targets. However, macrophages tested 3 to 5 days after immunization differed from those tested later, both in their kinetics of cytotoxicity and the type of target cell recognized. Thus, 5-day immune macrophages were cytotoxic for uninfected BHK and PARA-7 hamster tumor cells as well as BHKV and BHKH. In contrast, 9-day immune macrophages were cytotoxic for BHKV and BHKH, but not uninfected BHK or PARA-7. Also, in vitro assay kinetics showed that early 5-day immune macrophages were more rapidly cytotoxic for all target cells than late 9-day immune macrophages. This study also showed that nonadherent peritoneal exudate cells (NPEC) were induced by vaccinia immunization that were nonspecific in their cytotoxicity. Although both adherent macrophages and NPEC showed preferential lysis of virus-infected targets, the cytotoxicity mediated by NPEC was abrogated by treatment with NH4Cl, whereas macrophage cytotoxicity was not affected by such treatment. In summary, this study demonstrates that with time after immunization with vaccinia virus peritoneal macrophages differ markedly in their cytotoxicity characteristics with respect to target cell recognition and rate of target cell killing. Possible models to explain preferential cytotoxicity against virus-infected targets by late vaccinia immune macrophages are discussed.