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Cognate antigen directs CD8+ T cell migration to vascularized transplants
Jeffrey M. Walch, … , Geoffrey Camirand, Fadi G. Lakkis
Jeffrey M. Walch, … , Geoffrey Camirand, Fadi G. Lakkis
Published May 15, 2013
Citation Information: J Clin Invest. 2013;123(6):2663-2671. https://doi.org/10.1172/JCI66722.
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Research Article

Cognate antigen directs CD8+ T cell migration to vascularized transplants

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Abstract

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 Gαi-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 Gαi 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 Gαi, 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.

Authors

Jeffrey M. Walch, Qiang Zeng, Qi Li, Martin H. Oberbarnscheidt, Rosemary A. Hoffman, Amanda L. Williams, David M. Rothstein, Warren D. Shlomchik, Jiyun V. Kim, Geoffrey Camirand, Fadi G. Lakkis

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Figure 1

Gαi-independent migration of memory and effector T cells to heart allografts.

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Gαi-independent migration of memory and effector T cells to heart allogr...
PTx-treated and untreated T cells were cotransferred to heart allograft recipients 2 days after transplantation, except where indicated. (A and B) Enumeration of transferred memory CD8+ T cells in the grafts (A) and lymph nodes (B) of B6 recipients. T cell proliferation is shown in the CFSE histograms. (C and D) Enumeration and proliferation of transferred memory CD8+ T cells in splenectomized aly/aly recipient grafts. Memory T cells were transferred either 2 days (C) or 50 days (D) after transplantation. (E) Enumeration of effector, naive, and natural memory CD8+ T cells in B6 recipient grafts. (F) Heart allograft survival in splenectomized aly/aly recipients that received either PTx-treated (n = 4) or untreated (n = 4) memory T cells. Results are mean ± SEM. **P < 0.01; ***P < 0.001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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