HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Topham, D. J. Articles by Doherty, P. C. Search for Related Content PubMed PubMed Citation Articles by Topham, D. J. Articles by Doherty, P. C. Agricola Articles by Topham, D. J. Articles by Doherty, P. C.

Perforin and Fas in murine gammaherpesvirus-specific CD8⁺ T cell control and morbidity

Department of Immunology, St Jude Children’s Research Hospital, 332 North Lauderdale, Memphis, TN 38101, USA¹

Author for correspondence: David Topham. Present address: David H. Smith Center for Vaccine Biology & Immunology, Aab Institute for Biomedical Sciences, University of Rochester Medical Center, 601 Elmwood Avenue, Box 609, Rochester, NY 14642-8609, USA. Fax +1 716 273 2452. e-mail david_topham{at}urmc.rochester.edu

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 (HV-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- 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.

This article has been cited by other articles:

				P. Dias, A. L. Shea, C. Inglis, F. Giannoni, L. N. Lee, and S. R. Sarawar Primary Clearance of Murine Gammaherpesvirus 68 by PKC{theta}-/- CD8 T Cells Is Compromised in the Absence of Help from CD4 T Cells J. Virol., December 1, 2008; 82(23): 11970 - 11975. [Abstract] [Full Text] [PDF]

				F. Giannoni, A. Shea, C. Inglis, L. N. Lee, and S. R. Sarawar CD40 Engagement on Dendritic Cells, but Not on B or T Cells, Is Required for Long-Term Control of Murine Gammaherpesvirus 68 J. Virol., November 15, 2008; 82(22): 11016 - 11022. [Abstract] [Full Text] [PDF]

				E. S. Barton, M. L. Lutzke, R. Rochford, and H. W. Virgin IV Alpha/Beta Interferons Regulate Murine Gammaherpesvirus Latent Gene Expression and Reactivation from Latency J. Virol., November 15, 2005; 79(22): 14149 - 14160. [Abstract] [Full Text] [PDF]

				B. J. Lee, F. Giannoni, A. Lyon, S. Yada, B. Lu, C. Gerard, and S. R. Sarawar Role of CXCR3 in the Immune Response to Murine Gammaherpesvirus 68 J. Virol., July 15, 2005; 79(14): 9351 - 9355. [Abstract] [Full Text] [PDF]

				F. Giannoni, A. B. Lyon, M. D. Wareing, P. B. Dias, and S. R. Sarawar Protein Kinase C {theta} Is Not Essential for T-Cell-Mediated Clearance of Murine Gammaherpesvirus 68 J. Virol., June 1, 2005; 79(11): 6808 - 6813. [Abstract] [Full Text] [PDF]

				A. B. Kamath, J. Woodworth, X. Xiong, C. Taylor, Y. Weng, and S. M. Behar Cytolytic CD8+ T Cells Recognizing CFP10 Are Recruited to the Lung after Mycobacterium tuberculosis Infection J. Exp. Med., December 6, 2004; 200(11): 1479 - 1489. [Abstract] [Full Text] [PDF]

				M. B. Jordan, D. Hildeman, J. Kappler, and P. Marrack An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder Blood, August 1, 2004; 104(3): 735 - 743. [Abstract] [Full Text] [PDF]

				S. Andreansky, H. Liu, H. Adler, U. H. Koszinowski, S. Efstathiou, and P. C. Doherty The limits of protection by "memory" T cells in Ig-/- mice persistently infected with a {gamma}-herpesvirus PNAS, February 17, 2004; 101(7): 2017 - 2022. [Abstract] [Full Text] [PDF]

				H. Liu, S. Andreansky, G. Diaz, T. Hogg, and P. C. Doherty Reduced Functional Capacity of CD8+ T Cells Expanded by Post-Exposure Vaccination of {gamma}-Herpesvirus-Infected CD4-Deficient Mice J. Immunol., April 1, 2002; 168(7): 3477 - 3483. [Abstract] [Full Text] [PDF]

				R. M. Licon Luna, E. Lee, A. Mullbacher, R. V. Blanden, R. Langman, and M. Lobigs Lack of both Fas Ligand and Perforin Protects from Flavivirus-Mediated Encephalitis in Mice J. Virol., March 7, 2002; 76(7): 3202 - 3211. [Abstract] [Full Text] [PDF]