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Article
IFN-Induced Attrition of CD8 T Cells in the Presence or Absence of Cognate Antigen during the Early Stages of Viral Infections
The Journal of Immunology
  • Kapil Bahl
  • Sung-Kwon Kim
  • Claudia Calcagno, University of Genoa
  • Dario Ghersi, University of Nebraska at Omaha
  • Roberto Puzone
  • Franco Celada, University of Genoa
  • Liisa K. Selin, University of Massachusetts Medical School
  • Raymond M. Welsh, University of Massachusetts Medical School
Document Type
Article
Publication Date
4-1-2006
Abstract
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.
Citation Information
Kapil Bahl, Sung-Kwon Kim, Claudia Calcagno, Dario Ghersi, et al.. "IFN-Induced Attrition of CD8 T Cells in the Presence or Absence of Cognate Antigen during the Early Stages of Viral Infections" The Journal of Immunology Vol. 176 Iss. 7 (2006) p. 4284 - 4295
Available at: http://works.bepress.com/dario-ghersi/6/