| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,¶,¶
,¶
* Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655;
Valeant Pharmaceuticals International, Costa Mesa, CA 92626;
Department of Clinical Epidemiology, National Institute for Cancer Research, and
Department of Oncology, Biology and Genetics, University of Genoa, Genoa, Italy; and
¶ Department of Rheumatology, Hospital for Joint Diseases, New York, NY 10003
Profound lymphopenia has been observed during many acute viral infections, and our laboratory has previously documented a type I IFN-dependent loss of CD8 T cells immediately preceding the development of the antiviral T cell response. Most memory (CD44high) and some naive (CD44low) CD8 T cells are susceptible to IFN-induced attrition, and we show in this study that the IFN-induced attrition of CD8+CD44high T cells is associated with elevated activation of caspase-3 and caspase-8. We questioned whether TCR engagement by Ag would render CD8 T cells resistant to attrition. We tested whether a high concentration of Ag (GP33 peptide) would protect lymphocytic choriomeningitis (LCMV)-specific naive CD8 T cells (TCR transgenic P14 cells specific for the GP33 epitope of LCMV) and memory CD8 T cells (GP33-specific LCMV-immune cells) from depletion. Both naive P14 and memory GP33-specific donor CD8 T cells decreased substantially 16 h after inoculation with the Toll receptor agonist and IFN inducer, poly(I:C), regardless of whether a high concentration of GP33 peptide was administered to host mice beforehand. Moreover, donor naive P14 and LCMV-specific memory cells were depleted from day 2 LCMV-infected hosts by 16 h posttransfer. These results indicate that Ag engagement does not protect CD8 T cells from the IFN-induced T cell attrition associated with viral infections. In addition, computer models indicated that early depletion of memory T cells may allow for the generation for a more diverse T cell response to infection by reducing the immunodomination caused by cross-reactive T cells.
This article has been cited by other articles:
|
|
 |
|
  J.-Y. Zhang, Z. Zhang, B. Jin, S.-Y. Zhang, C.-B. Zhou, J.-L. Fu, and F.-S. Wang Cutting Edge: Programmed Death-1 Up-Regulation Is Involved in the Attrition of Cytomegalovirus-Specific CD8+ T Cells in Acute Self-Limited Hepatitis B Virus Infection J. Immunol., September 15, 2008; 181(6): 3741 - 3744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Bradfute, K. L. Warfield, and S. Bavari Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection J. Immunol., March 15, 2008; 180(6): 4058 - 4066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. C. Ireland, S. A. Stohlman, D. R. Hinton, R. Atkinson, and C. C. Bergmann Type I Interferons Are Essential in Controlling Neurotropic Coronavirus Infection Irrespective of Functional CD8 T Cells J. Virol., January 1, 2008; 82(1): 300 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Goulding, R. Snelgrove, J. Saldana, A. Didierlaurent, M. Cavanagh, E. Gwyer, J. Wales, E. L. Wissinger, and T. Hussell Respiratory Infections: Do We Ever Recover? Proceedings of the ATS, December 1, 2007; 4(8): 618 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Thornley, N. E. Phillips, B. C. Beaudette-Zlatanova, T. G. Markees, K. Bahl, M. A. Brehm, L. D. Shultz, E. A. Kurt-Jones, J. P. Mordes, R. M. Welsh, et al. Type 1 IFN Mediates Cross-Talk between Innate and Adaptive Immunity That Abrogates Transplantation Tolerance J. Immunol., November 15, 2007; 179(10): 6620 - 6629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Stoltz, C. Ahlm, A. Lundkvist, and J. Klingstrom Lambda Interferon (IFN-{lambda}) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-{gamma}-Induced Nitric Oxide Production J. Virol., August 15, 2007; 81(16): 8685 - 8691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hosmalin and P. Lebon Type I interferon production in HIV-infected patients J. Leukoc. Biol., November 1, 2006; 80(5): 984 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. McBride, K. Hoebe, P. Georgel, and E. Janssen Cell-Associated Double-Stranded RNA Enhances Antitumor Activity through the Production of Type I IFN J. Immunol., November 1, 2006; 177(9): 6122 - 6128. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
