Vaccinia Virus Inhibits T Cell Receptor–Dependent Responses by Human γδ T Cells (original) (raw)
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Inhibition of CD1d1-mediated antigen presentation by vaccinia virus B1R and H5R molecules
Vaccinia virus (VV) has been most commonly used as the vaccine to protect individuals against the causative agent of smallpox (variola virus), but it also uses a number of strategies meant to evade or blunt the host's antiviral immune response. Natural killer T (NKT) cells are a subset of immunoregulatory CD1d-restricted T lymphocytes believed to bridge the innate and adaptive immune responses. It is shown here that the VVencoded molecules, B1R and H5R, play a role in the ability of VV to inhibit CD1dmediated antigen presentation to NKT cells. These are the first poxvirus-encoded molecules identified that can play such a role in the evasion of an important component of the innate immune response.
Inhibition of CD1d1-Mediated Antigen Presentation by the Vaccinia Virus B1R and H5R Molecules
European journal …, 2006
Vaccinia virus (VV) has been most commonly used as the vaccine to protect individuals against the causative agent of smallpox (variola virus), but it also uses a number of strategies meant to evade or blunt the host's antiviral immune response. Natural killer T (NKT) cells are a subset of immunoregulatory CD1d-restricted T lymphocytes believed to bridge the innate and adaptive immune responses. It is shown here that the VVencoded molecules, B1R and H5R, play a role in the ability of VV to inhibit CD1dmediated antigen presentation to NKT cells. These are the first poxvirus-encoded molecules identified that can play such a role in the evasion of an important component of the innate immune response.
Vaccinia Virus in Human Lymphoid Tissue Ex Vivo
2007
Vaccinia virus (VACV) has been attracting attention recently not only as a vector for various vaccines but also as an immunization tool against smallpox because of its potential use as a bioterrorism agent. It has become evident that in spite of a long history of studies of VACV, its tissue pathogenesis remains to be fully understood. Here, we investigated the pathogenesis of VACV and its interactions with human immunodefi-ciency virus type 1 (HIV-1) in the context of human lymphoid tissues. We found that ex vivo-cultured tonsillar tissue supports productive infection by the New York City Board of Health strain, the VACV strain of the Dryvax vaccine. VACV readily infected both T and non-T (B) lymphocytes and depleted cells of both of these subsets equally over a 12-day period postinfection. Among T lymphocytes, CD8 cells are preferentially depleted in accordance with their preferential infection: the probability that a CD8 T cell will be productively infected is almost six times hig...
Cellular and Humoral Immunity against Vaccinia Virus Infection of Mice
The Journal of Immunology, 2004
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-␥ 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.
Journal of Virology, 2005
Poxvirus vaccine vectors, although capable of eliciting potent immune responses, pose serious health risks in immunosuppressed individuals. We therefore constructed five novel recombinant vaccinia virus vectors which contained overlapping deletions of coding regions for the B5R, B8R, B12R, B13R, B14R, B16R, B18R, and B19R immunomodulatory gene products and assessed them for both immunogenicity and pathogenicity. All five of these novel vectors elicited both cellular and humoral immunity to the inserted HIV-BH10 env comparable to that induced by the parental Wyeth strain vaccinia virus. However, deletion of these immunomodulatory genes did not increase the immunogenicity of these vectors compared with the parental vaccinia virus. Furthermore, four of these vectors were slightly less virulent and one was slightly more virulent than the Wyeth strain virus in neonatal mice. Attenuated poxviruses have potential use as safer alternatives to current replication-competent vaccinia virus. Improved vaccinia virus vectors can be generated by deleting additional genes to achieve a more significant viral attenuation.
Innate Immunity to Viruses: Control of Vaccinia Virus Infection by γδ T Cells
The Journal of Immunology, 2001
The existence of γδ T cells has been known for over 15 years, but their significance in innate immunity to virus infections has not been determined. We show here that γδ T cells are well suited to provide a rapid response to virus infection and demonstrate their role in innate resistance to vaccinia virus (VV) infection in both normal C57BL/6 and β TCR knockout (KO) mice. VV-infected mice deficient in γδ T cells had significantly higher VV titers early postinfection (PI) and increased mortality when compared with control mice. There was a rapid and profound VV-induced increase in IFN-γ-producing γδ T cells in the peritoneal cavity and spleen of VV-infected mice beginning as early as day 2 PI. This rapid response occurred in the absence of priming, as there was constitutively a significant frequency of VV-specific γδ T cells in the spleen in uninfected β TCR KO mice, as demonstrated by limiting dilution assay. Also, like NK cells, another mediator of innate immunity to viruses, γδ T ...