title: Increased protection from vaccinia virus infection in mice genetically prone to lymphoproliferative disorders.
abstract: Mutations in the genes that encode Fas or Fas ligand (FasL) can result in poor restraints on lymphocyte activation and in increased susceptibility to autoimmune disorders. Because these mutations portend a continuously activated immune state, we hypothesized that they might in some cases confer resistance to infection. To examine this possibility, the immune response to, morbidity caused by, and clearance of vaccinia virus (VACV) Western Reserve was examined in 5- to 7-week-old Fas mutant (lpr) mice, before an overt lymphoproliferative disorder was observable. On day 6 after VACV infection, C57BL/6-lpr (B6-lpr) mice had decreased morbidity, decreased viral titers, and an increased percentage and number of CD4(+) and CD8(+) T cells. As early as day 2 after infection, B6-lpr mice had decreased liver and spleen viral titers and increased numbers of and increased gamma interferon (IFN-γ) production by several different effector cell populations. Depletion of individual effector cell subsets did not inhibit the resistance of B6-lpr mice. Uninfected B6-lpr mice also had increased numbers of NK cells, γδ(+) T cells, and CD44(+) CD4(+) and CD44(+) CD8(+) T cells compared to uninfected B6 mice. Antibody to IFN-γ resulted in increased virus load in both B6 and B6-lpr mice and eliminated the differences in viral titers between them. These results suggest that IFN-γ produced by multiple activated leukocyte populations in Fas-deficient hosts enhances resistance to some viral infections.
authors.affiliation: Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Mina O
authors.initials: MO
authors.lastname: Seedhom
authors.forename: Keisha S
authors.initials: KS
authors.lastname: Mathurin
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Kim
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Welsh
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D060467:Disease Resistance; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000821:virology; D016131:Lymphocyte Subsets / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000150:complications* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000821:virology; D016019:Survival Analysis; D014615:Vaccinia / Q000276:immunology / Q000401:mortality* / Q000821:virology*; D014616:Vaccinia virus / Q000276:immunology / Q000472:pathogenicity*; D019562:Viral Load; D019014:fas Receptor / Q000172:deficiency*
chemical_list: D019014:fas Receptor; D007371:Interferon-gamma