Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and morbidity. Export

@article{citeulike:2702778, abstract = {The immune system uses both virus-specific T cells and B cells to control the acute and latent phases of respiratory infection with the murine gammaherpesvirus 68 (gammaHV-68). We sought to further define the important effector mechanisms for CD8(+) T cells. First, depletion of the CD4(+) T cells resulted in a failure of most animals to drive the virus into latency, although lytic virus in the lung was reduced by approximately 1000-fold from its peak. Second, the absence of either perforin or Fas alone had no impact on the ability to reduce titres of lytic virus in the lung. Further neutralization of IFN-gamma in CD4-depleted P(+/+), P(-/-) or Fas(-/-) mice had no effect. To define the requirements for Fas or perforin more clearly, two sets of chimeric mice were constructed differing in perforin expression by the T cells, and Fas on infected epithelial cells or lymphocytes. Animals with P(-/-) T cells and a Fas(-/-) lung failed to limit the shedding of infectious virus, regardless of whether CD4 T cells were present. In addition, we noted that having P(-/-) T cells in irradiated Fas(+/+) hosts caused a lethal disease that was not apparent in the non-chimeric (unirradiated) P(-/-) (Fas(+/+)) mice. In another set of chimeric mice, P(-/-) T cells were able to limit persistent infection of B cells that expressed Fas, but not B cells that were Fas-deficient. These studies demonstrate that some degree of cytotoxicity via either perforin or Fas is essential for CD8(+) T cells to control this DNA virus.}, address = {Department of Immunology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38101, USA. david\_topham@urmc.rochester.edu}, author = {Topham, D. J. and Cardin, R. C. and Christensen, J. P. and Brooks, J. W. and Belz, G. T. and Doherty, P. C.}, citeulike-article-id = {2702778}, citeulike-linkout-0 = {http://vir.sgmjournals.org/cgi/content/abstract/82/8/1971}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11458005}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11458005}, comment = {Everything is measured in respect to lung titers. not any 2ndary lymphoid tissues. ---=note-separator=--- also, almost everything is lytic replication}, issn = {0022-1317}, journal = {The Journal of general virology}, keywords = {fas, granzymeb, mhv68, perforin}, month = {August}, number = {Pt 8}, pages = {1971--1981}, posted-at = {2008-04-22 20:12:26}, priority = {5}, title = {Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and morbidity.}, url = {http://vir.sgmjournals.org/cgi/content/abstract/82/8/1971}, volume = {82}, year = {2001} }

TY - JOUR ID - citeulike:2702778 L3 - citeulike-article-id:2702778 N2 - The immune system uses both virus-specific T cells and B cells to control the acute and latent phases of respiratory infection with the murine gammaherpesvirus 68 (gammaHV-68). We sought to further define the important effector mechanisms for CD8(+) T cells. First, depletion of the CD4(+) T cells resulted in a failure of most animals to drive the virus into latency, although lytic virus in the lung was reduced by approximately 1000-fold from its peak. Second, the absence of either perforin or Fas alone had no impact on the ability to reduce titres of lytic virus in the lung. Further neutralization of IFN-gamma in CD4-depleted P(+/+), P(-/-) or Fas(-/-) mice had no effect. To define the requirements for Fas or perforin more clearly, two sets of chimeric mice were constructed differing in perforin expression by the T cells, and Fas on infected epithelial cells or lymphocytes. Animals with P(-/-) T cells and a Fas(-/-) lung failed to limit the shedding of infectious virus, regardless of whether CD4 T cells were present. In addition, we noted that having P(-/-) T cells in irradiated Fas(+/+) hosts caused a lethal disease that was not apparent in the non-chimeric (unirradiated) P(-/-) (Fas(+/+)) mice. In another set of chimeric mice, P(-/-) T cells were able to limit persistent infection of B cells that expressed Fas, but not B cells that were Fas-deficient. These studies demonstrate that some degree of cytotoxicity via either perforin or Fas is essential for CD8(+) T cells to control this DNA virus. IS - Pt 8 JF - The Journal of general virology SN - 0022-1317 AD - Department of Immunology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38101, USA. david_topham@urmc.rochester.edu EP - 1981 TI - Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and morbidity. VL - 82 SP - 1971 KW - fas KW - granzymeb KW - mhv68 KW - perforin N1 - Everything is measured in respect to lung titers. not any 2ndary lymphoid tissues. N1 - also, almost everything is lytic replication AU - Topham, DJ AU - Cardin, RC AU - Christensen, JP AU - Brooks, JW AU - Belz, GT AU - Doherty, PC PY - 2001/08// UR - http://vir.sgmjournals.org/cgi/content/abstract/82/8/1971 ER -