GSBS Student Publications

Title

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

UMMS Affiliation

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

Date

8-18-2000

Document Type

Article

Medical Subject Headings

Animals; Antibodies, Monoclonal; Blood Transfusion; CD40 Ligand; CD8-Positive T-Lymphocytes; Female; *Immune Tolerance; *Lymphocyte Depletion; Lymphocytic Choriomeningitis; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Skin Transplantation; Transplantation, Homologous

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: J Surg Res. 2000 Sep;93(1):63-9. Link to article on publisher's site

DOI of Published Version

10.1006/jsre.2000.5962

Related Resources

Link to Article in PubMed

Journal Title

The Journal of surgical research

PubMed ID

10945944