Viral infection abrogates CD8(+) T-cell deletion induced by costimulation blockade.
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.
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- Transplantation, Homologous
- Surgery
- Skin Transplantation
- Mice, Inbred CBA
- Mice, Inbred C57BL
- Mice
- Membrane Glycoproteins
- Male
- Lymphocytic Choriomeningitis
- Lymphocyte Depletion
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transplantation, Homologous
- Surgery
- Skin Transplantation
- Mice, Inbred CBA
- Mice, Inbred C57BL
- Mice
- Membrane Glycoproteins
- Male
- Lymphocytic Choriomeningitis
- Lymphocyte Depletion