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  • Microbiology Society  (3)
  • 1
    Online Resource
    Online Resource
    Microbiology Society ; 2004
    In:  Journal of General Virology Vol. 85, No. 10 ( 2004-10-01), p. 3017-3026
    In: Journal of General Virology, Microbiology Society, Vol. 85, No. 10 ( 2004-10-01), p. 3017-3026
    Abstract: A CD8 + T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant K d -restricted epitope from the viral transcription anti-terminator protein M2 (M2 82–90 ), linked covalently to human β 2 -microglobulin ( β 2 m). Cutaneous gene-gun immunization of BALB/c mice with this construct induced an antigen-specific CD8 + T-cell memory. After intranasal RSV challenge, accelerated CD8 + T-cell responses were observed in pulmonary lymph nodes and virus clearance from the lungs was enhanced. The construct induced weaker CD8 + T-cell responses than those elicited with recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger than those induced by a similar DNA construct without the β 2 m gene. DNA vaccination led to enhanced pulmonary disease after RSV challenge, with increased weight loss and cell recruitment to the lung. Depletion of CD8 + T cells reduced, but did not abolish, enhancement of disease. Mice vaccinated with a construct encoding a class I-restricted lymphocytic choriomeningitis virus epitope and β 2 m suffered more severe weight loss after RSV infection than unvaccinated RSV-infected mice, although RSV-specific CD8 + T-cell responses were not induced. Thus, in addition to specific CD8 + T cell-mediated immunopathology, gene-gun DNA vaccination causes non-specific enhancement of RSV disease without affecting virus clearance.
    Type of Medium: Online Resource
    ISSN: 0022-1317 , 1465-2099
    RVK:
    RVK:
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2004
    detail.hit.zdb_id: 2007065-2
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Microbiology Society ; 2002
    In:  Journal of General Virology Vol. 83, No. 9 ( 2002-09-01), p. 2123-2133
    In: Journal of General Virology, Microbiology Society, Vol. 83, No. 9 ( 2002-09-01), p. 2123-2133
    Abstract: Using infections with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus in mice as model systems, we have investigated the ability of antigen-primed CD8 + T cells generated in the context of viral infections to produce IL-2. Our results indicate that acute immunizing infection normally leads to generation of high numbers of IL-2-producing antigen-specific CD8 + T cells. By costaining for IL-2 and IFN-γ intracellularly, we found that IL-2-producing cells predominantly constitute a subset of cells also producing IFN-γ. Comparison of the kinetics of generation revealed that IL-2-producing cells appear slightly delayed compared with the majority of IFN-γ producing cells, and the relative frequency of the IL-2-producing subset increases with transition into the memory phase. In contrast to acute immunizing infection, few IL-2-producing cells are generated during chronic LCMV infection. Furthermore, in MHC class II-deficient mice, which only transiently control LCMV infection, IL-2-producing CD8 + T cells are initially generated, but by 4 weeks after infection this subset has nearly disappeared. Eventually the capacity to produce IFN-γ also becomes impaired, while cell numbers are maintained at a level similar to those in wild-type mice controlling the infection. Taken together, these findings indicate that phenotyping of T cell populations based on capacity to produce cytokines, and especially IL-2, can provide important information as to the functional status of the analysed cell subset. Specifically, combined analysis of the capacity to produce IL-2 and IFN-γ can be used as a predictor for loss of function within the CD8 + T cell compartment.
    Type of Medium: Online Resource
    ISSN: 0022-1317 , 1465-2099
    RVK:
    RVK:
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2002
    detail.hit.zdb_id: 2007065-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    Online Resource
    Online Resource
    Microbiology Society ; 2004
    In:  Journal of General Virology Vol. 85, No. 6 ( 2004-06-01), p. 1703-1712
    In: Journal of General Virology, Microbiology Society, Vol. 85, No. 6 ( 2004-06-01), p. 1703-1712
    Abstract: The ability of virus-specific CD8 + T cells to produce cytokines was studied in mice infected with lymphocytic choriomeningitis virus and vesicular stomatitis virus. Intracellular staining was used to visualize cytokine-producing CD8 + and CD4 + T cells. Overall, virus-specific CD8 + T cells produce a similar range of cytokines (IFN- γ , TNF- α , IL-2, GM-CSF, RANTES, MIP-1 α and MIP-1 β ) as CD4 + T cells, but the relative distribution of cytokine-producing subsets is different. Moreover, cytokine-producing CD8 + T cells were found to dominate numerically at all time-points tested. Co-staining for more than one cytokine revealed that while all cytokine-producing CD8 + T cells synthesized IFN- γ , additional cytokines were produced by partly overlapping subsets of this population. The frequency of cells producing more than one cytokine was higher in a tertiary site (peritoneum) and generally increased with transition into the memory phase; however, GM-CSF producing cells were only present transiently. Concerning factors predicted to influence the distribution of cytokine-producing subsets, IFN- γ and IL-12 did not play a role, nor was extensive virus replication essential. Notably, regarding the heterogeneity in cytokine production by individual cells with similar epitope specificity, variation in TCR avidity was not the cause, since in vivo -activated TCR transgene-expressing cells were as heterogeneous in cytokine expression as polyclonal cells specific for the same epitope.
    Type of Medium: Online Resource
    ISSN: 0022-1317 , 1465-2099
    RVK:
    RVK:
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2004
    detail.hit.zdb_id: 2007065-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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