Cellular and Humoral Immunity against Vaccinia Virus Infection of Mice

Abstract

Despite the widespread use of vaccinia virus (VV) as a vector for other Ags and as the smallpox vaccine, there is little information available about the protective components of the immune response following VV infection. In this study, protection against wild-type VV was evaluated in mice with respect to the relative contributions of CD8+ T cells vs that of CD4+ T cells and Ab. C57BL/6 mice primed with the Western Reserve strain of VV mount significant IgM and IgG Ab responses, specific cytotoxic T cell responses, IFN-γ responses in CD4+ and CD8+ T cells, and effectively clear the virus. This protection was abrogated by in vivo depletion of CD4+ T cells or B cells in IgH−/− mice, but was not sensitive to CD8+ T cell depletion alone. However, a role for CD8+ T cells in primary protection was demonstrated in MHC class II−/− mice, where depleting CD8+ T cells lead to increase severity of disease. Unlike control MHC class II−/− mice, the group depleted of CD8+ T cells developed skin lesions on the tail and feet and had adrenal necrosis. Adoptive transfer experiments also show CD8+ T cells can mediate protective memory. These results collectively show that both CD4+ and CD8+ T cell-mediated immunity can contribute to protection against VV infection. However, CD4+ T cell-dependent anti-virus Ab production plays a more important role in clearing virus following acute infection, while in the absence of Ab, CD8+ T cells can contribute to protection against disease.

Vaccination of BALB/c Mice withEscherichia coli-Expressed Vaccinia Virus Proteins A27L, B5R, and D8L Protects Mice from Lethal Vaccinia Virus Challenge

“…In addition, passive transfer of vaccinia virus immune sera obtained from vaccinated animals was shown to be protective (3,10,30). T cells, however, can provide protection necessary for survival and recovery in the absence of effective antibody responses (3,56). These studies indicate that both cellular and humoral responses can contribute to optimal protection against vaccinia virus.…”

“…Not only can these CD4 ϩ T cells potentially provide help for enhanced humoral (53) and CD8 ϩ T-cell (44) responses, but they may also have direct antiviral activity (33). The CD8 ϩ T cells may be involved in direct killing of virus-infected cells and may contribute significantly to survival and recovery from virus challenge in the absence of humoral responses (3,56). No B5R 14/15-or D8L 12/13-specific CD8 ϩ T cells from A27L-, D8L-, and B5R-vaccinated mice were detected, indicating that immunization with these recombinant proteins does not lead to the generation of significant CD8 ϩ T-cell responses.…”

Vaccinia virus infection induces dendritic cell maturation but inhibits antigen presentation by MHC class II

“…In this case, however, the virus appears to have altered antigen processing in an epitope specific manner. Less is known regarding MHC class II mediated antigen presentation during a VV infection, although CD4 T cell responses are also thought to be critical in promoting viral clearance and immunity [11]. Mice deficient in MHC class II protein expression displayed slightly decreased cytotoxic T lymphocyte (CTL) responses against VV [12].…”

A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection

“…The double-stranded DNA genome is ϳ195 kb long and is predicted to encode at least 218 open reading frames (ORF; GenBank accession number AY243312). The adaptive immune response to poxviruses involves B cells as well as both CD4 ϩ and CD8 ϩ T cells (2,3). Adoptive transfer experiments have shown that CD8 ϩ T cells can mediate control of VACV infection.…”