title: Comparable polyfunctionality of ectromelia virus- and vaccinia virus-specific murine T cells despite markedly different in vivo replication and pathogenicity.
abstract: Vaccinia virus (VACV) stimulates long-term immunity against highly pathogenic orthopoxvirus infection of humans (smallpox) and mice (mousepox [ectromelia virus {ECTV}]) despite the lack of a natural host-pathogen relationship with either of these species. Previous research revealed that VACV is able to induce polyfunctional CD8(+) T-cell responses after immunization of humans. However, the degree to which the functional profile of T cells induced by VACV is similar to that generated during natural poxvirus infection remains unknown. In this study, we monitored virus-specific T-cell responses following the dermal infection of C57BL/6 mice with ECTV or VACV. Using polychromatic flow cytometry, we measured levels of degranulation, cytokine expression (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]), and the cytolytic mediator granzyme B. We observed that the functional capacities of T cells induced by VACV and ECTV were of a similar quality in spite of the markedly different replication abilities and pathogenic outcomes of these viruses. In general, a significant fraction (≥50%) of all T-cell responses were positive for at least three functions both during acute infection and into the memory phase. In vivo killing assays revealed that CD8(+) T cells specific for both viruses were equally cytolytic (∼80% target cell lysis after 4 h), consistent with the similar levels of granzyme B and degranulation detected among these cells. Collectively, these data provide a mechanism to explain the ability of VACV to induce protective T-cell responses against pathogenic poxviruses in their natural hosts and provide further support for the use of VACV as a vaccine platform able to induce polyfunctional T cells.
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Hersperger
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Siciliano
authors.forename: Laurence C
authors.initials: LC
authors.lastname: Eisenlohr
mesh_terms: D000818:Animals; D015550:Cell Degranulation; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D004481:Ectromelia virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D004482:Ectromelia, Infectious / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology
chemical_list: D016207:Cytokines; D053804:Granzymes