Memory T cells migrate to and reject vascularized cardiac allografts independent of the chemokine receptor CXCR3
MH Oberbarnscheidt, JM Walch, Q Li, AL Williams… - …, 2011 - journals.lww.com
MH Oberbarnscheidt, JM Walch, Q Li, AL Williams, JT Walters, RA Hoffman, AJ Demetris…
Transplantation, 2011•journals.lww.comBackground. Memory T cells migrate to and reject transplanted organs without the need for
priming in secondary lymphoid tissues, but the mechanisms by which they do so are not
known. Here, we tested whether CXCR3, implicated in the homing of effector T cells to sites
of infection, is critical for memory T-cell migration to vascularized allografts. Methods. CD4
and CD8 memory T cells were sorted from alloimmunized CXCR3−/− and wildtype B6 mice
and cotransferred to congenic B6 recipients of BALB/c heart allografts. Graft-infiltrating T …
priming in secondary lymphoid tissues, but the mechanisms by which they do so are not
known. Here, we tested whether CXCR3, implicated in the homing of effector T cells to sites
of infection, is critical for memory T-cell migration to vascularized allografts. Methods. CD4
and CD8 memory T cells were sorted from alloimmunized CXCR3−/− and wildtype B6 mice
and cotransferred to congenic B6 recipients of BALB/c heart allografts. Graft-infiltrating T …
Abstract
Background.
Memory T cells migrate to and reject transplanted organs without the need for priming in secondary lymphoid tissues, but the mechanisms by which they do so are not known. Here, we tested whether CXCR3, implicated in the homing of effector T cells to sites of infection, is critical for memory T-cell migration to vascularized allografts.
Methods.
CD4 and CD8 memory T cells were sorted from alloimmunized CXCR3−/− and wildtype B6 mice and cotransferred to congenic B6 recipients of BALB/c heart allografts. Graft-infiltrating T cells were quantitated 20 and 72 hr later by flow cytometry. Migration and allograft survival were also studied in splenectomized alymphoplastic (aly/aly) recipients, which lack secondary lymphoid tissues.
Results.
We found that polyclonal and antigen-specific memory T cells express high levels of CXCR3. No difference in migration of wildtype versus CXCR3−/− CD4 and CD8 memory T cells to allografts could be detected in wildtype or aly/aly hosts. In the latter, wildtype and CXCR3−/− memory T cells precipitated acute rejection at similar rates. Blocking CCR5, a chemokine receptor also upregulated on memory T cells, did not delay graft rejection mediated by CXCR3−/− memory T cells.
Conclusions.
CXCR3 is not critical for the migration of memory T cells to vascularized organ allografts. Blocking CXCR3 or CXCR3 and CCR5 does not delay acute rejection mediated by memory T cells. These findings suggest that the mechanisms of memory T cell-homing to transplanted organs may be distinct from those required for their migration to sites of infection.
Lippincott Williams & Wilkins