ABSTRACT
Cytotoxic activity attributable to natural killer (NK) cells was augmented in the spleens of mice infected with murine cytomegalovirus (MCMV). Stimulation was observed as early as 10 hr after virus administration but was dependent upon the dose used, and in particular, the host genotype. Effector cells were capable of killing a range of tumor cell targets as well as normal syngeneic thymocytes, and were induced in nude (nu/nu) and heterozygous (nu/+) mice. A significant correlation existed between resistance to the lethal effects of MCMV infection and the degree of NK cell augmentation by this virus in 10 of 11 strains examined. Non-H-2 related differences in activity were observed, but a clear association between high NK cell responses and the possession of a particular H-2 haplotype was not apparent. Beige mutant C57BL/6J mice, previously reported as defective in NK cell function were susceptible to MCMV and expressed low levels of cytotoxicity during infection. Thus, the genetically controlled stimulation of NK cells in the early stages of infection with MCMV may contribute to the genotype related patterns of resistance seen with this virus.
Subject(s)
Cytomegalovirus Infections/genetics , Cytotoxicity, Immunologic , Animals , Cytomegalovirus/immunology , Cytomegalovirus Infections/immunology , Dose-Response Relationship, Immunologic , Male , Mice , Mice, Inbred A , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Nude , Spleen/immunologyABSTRACT
Studies of the resistance patterns to infection with a murine cytomegalovirus in inbred strains of mice revealed the existence of resistant and susceptible strains. Resistance was found to be associated with possession of the H-2k allele at the major histocompatibility locus of the mouse. The F1 hybrid between a resistant strain (C3H/HeJ) and a susceptible strain (BALB/c) was found to have a resistance intermediate between that of both parents, indicating that the gene(s) controlling resistance is partly dominant. Susceptible BALB/c mice could be made resistant to lethal infection by pre-treatment with thioglycollate broth but not by pre-treatment with endotoxin or BCG. Resistant C3H/HeJ mice could be made susceptible to lethal infection by pre-treatment with cyclophosphamide.
Subject(s)
Alleles , Cytomegalovirus Infections/genetics , Histocompatibility , Animals , BCG Vaccine/therapeutic use , Cyclophosphamide/therapeutic use , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/immunology , Endotoxins/therapeutic use , Genes, Dominant , Hybridization, Genetic , Mice , Mice, Inbred Strains , Salmonella typhimurium , Species Specificity , Thioglycolates/therapeutic useABSTRACT
Mice were exposed for 7 to 8 minutes on weekdays to fresh smoke from high-tar (HT) or low-tar (LT) cigarettes for varying periods of up to 36 weeks. Mice exposed to HT cigarettes exhibited more marked alterations in humoral immune responsiveness, hematological profiles, and pulmonary pathologic findings than those exposed to LT cigarettes. However, cell-mediated immune responsiveness to both bacterial and tumor-specific antigens was depressed similarly in animals exposed to HT or LT cigarettes. Furthermore, the growth rates of subcutaneously established tumors were enhanced similarly in the two groups, with respect to those in control animals.
