Viral infection abrogates CD8(+) T-cell deletion induced by costimulation blockade.

Published

Journal Article

BACKGROUND: Treatment with a single donor-specific transfusion (DST) plus a brief course of anti-CD154 monoclonal antibody (mAb) prolongs skin allograft survival in mice. It is known that prolongation of allograft survival by this method depends in part on deletion of alloreactive CD8(+) T cells at the time of tolerance induction. Recent data suggest that infection with lymphocytic choriomeningitis virus (LCMV) abrogates the ability of this protocol to prolong graft survival. METHODS: To study the mechanism by which viral infection abrogates allograft survival, we determined (1) the fate of tracer populations of alloreactive transgenic CD8(+) T cells and (2) the duration of skin allograft survival following treatment with DST and anti-CD154 mAb in the presence or absence of LCMV infection. RESULTS: We confirmed that treatment of uninfected mice with DST and anti-CD154 mAb leads to the deletion of alloreactive CD8(+) T cells and is associated with prolongation of skin allograft survival. In contrast, treatment with DST and anti-CD154 mAb in the presence of intercurrent LCMV infection was associated with the failure to delete alloreactive CD8(+) T cells and with the rapid rejection of skin allografts. The number of alloreactive CD8(+) cells actually increased significantly, and the cells acquired an activated phenotype. CONCLUSIONS: Interference with the deletion of alloreactive CD8(+) T cells mediated by DST and anti-CD154 mAb may in part be the mechanism by which viral infection abrogates transplantation tolerance induction.

Full Text

Duke Authors

Cited Authors

  • Turgeon, NA; Iwakoshi, NN; Phillips, NE; Meyers, WC; Welsh, RM; Greiner, DL; Mordes, JP; Rossini, AA

Published Date

  • September 2000

Published In

Volume / Issue

  • 93 / 1

Start / End Page

  • 63 - 69

PubMed ID

  • 10945944

Pubmed Central ID

  • 10945944

International Standard Serial Number (ISSN)

  • 0022-4804

Digital Object Identifier (DOI)

  • 10.1006/jsre.2000.5962

Language

  • eng

Conference Location

  • United States