The exposure postoperatively of patients who have undergone spinal surgery to increased amounts of natural sunlight during their hospital recovery period may result in decreased stress, pain, analgesic medication use, and pain medication costs.

The migration of effector or memory T cells to the graft is a critical event in the rejection of transplanted organs. The prevailing view is that the key steps involved in T cell migration -integrin-mediated firm adhesion followed by transendothelial migration -are dependent on the activation of Gα i -coupled chemokine receptors on T cells. In contrast to this view, we demonstrated in vivo that cognate antigen was necessary for the firm adhesion and transendothelial migration of CD8 + effector T cells specific to graft antigens and that both steps occurred independent of Gα i signaling. Presentation of cognate antigen by either graft endothelial cells or bone marrow-derived APCs that extend into the capillary lumen was sufficient for T cell migration. The adhesion and transmigration of antigen-nonspecific (bystander) effector T cells, on the other hand, remained dependent on Gα i , but required the presence of antigen-specific effector T cells. These findings underscore the primary role of cognate antigen presented by either endothelial cells or bone marrow-derived APCs in the migration of T cells across endothelial barriers and have important implications for the prevention and treatment of graft rejection.

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 co-transferred to congenic B6 recipients of BALB/c heart allografts. Graft-infiltrating T cells were quantitated 20 and 72 hours 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 vs CXCR3−/− CD4 and CD8 memory T cells to allografts could be detected in either 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 either 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.

Antigen-driven migration of effector and memory T cells sheds new light on the pathogenesis of transplant rejection and predicts that interrupting the TCR-triggered 'inside-out' signaling pathway, rather than that initiated by Gαi-coupled chemokine receptors, is a key approach to preventing rejection.