Viral infection abrogates CD8(+) T-cell deletion induced by costimulation blockade
Graduate School of Biomedical Sciences; >Department of Medicine, Division of Diabetes; Department of Medicine, Division of Endocrinology and Metabolism; Department of Pathology; Department of Surgery
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Surg Res. 2000 Sep;93(1):63-9. Link to article on publisher's site
The Journal of surgical research
Turgeon, Nicole A.; Iwakoshi, Neal N.; Phillips, Nancy E.; Meyers, William C.; Welsh, Raymond M.; Greiner, Dale L.; Mordes, John P.; and Rossini, Aldo A., "Viral infection abrogates CD8(+) T-cell deletion induced by costimulation blockade" (2000). GSBS Student Publications. 1268.