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CD4+ T lymphocytes produce adiponectin in response to transplants
Sreedevi Danturti, Karen S. Keslar, Leah R. Steinhoff, Ran Fan, Nina Dvorina, Anna Valujskikh, Robert L. Fairchild, William M. Baldwin III
Sreedevi Danturti, Karen S. Keslar, Leah R. Steinhoff, Ran Fan, Nina Dvorina, Anna Valujskikh, Robert L. Fairchild, William M. Baldwin III
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Research Article Inflammation Transplantation

CD4+ T lymphocytes produce adiponectin in response to transplants

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Abstract

Adiponectin is a pleiotropic cytokine with diverse immunomodulatory effects on macrophages and lymphocytes. In the current paradigm, lymphocytes and macrophages respond to adiponectin that is produced by adipocytes and other parenchymal cells. Using a model of chronic arterial inflammation in cardiac transplants, we found that T cells derived from the recipient migrate to the heart and produce adiponectin locally. The evidence that T cells produce significant amounts of adiponectin is based on 3 experimental approaches. First, CD4+ T cells isolated from the blood and spleen after cardiac transplantation express mRNA for adiponectin. Second, reconstitution of T cell–deficient recipients with transgenic CD4+ T cells that express receptors for donor antigens results in arterial infiltrates containing T cells and increased mRNA expression for adiponectin in cardiac transplants. Third, CD4+ T cells isolated from the allograft secrete adiponectin in vitro. Taken together, these data indicate that adiponectin-competent cells originating in the recipient migrate into the transplant. Establishing T cells as a source of adiponectin provides a new dimension, to our knowledge, to the modulatory effects of adiponectin on immune responses.

Authors

Sreedevi Danturti, Karen S. Keslar, Leah R. Steinhoff, Ran Fan, Nina Dvorina, Anna Valujskikh, Robert L. Fairchild, William M. Baldwin III

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Figure 5

Adiponectin message and protein is expressed by T cells isolated from blood, spleen, and allografts.

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Adiponectin message and protein is expressed by T cells isolated from bl...
(A) Adiponectin message in circulating CD4+ and CD8+ T cells isolated by negative magnetic bead separation from blood (open squares) and spleen (open diamond) of WT recipients of WT allografts. Bars indicate ± SEM with significant differences (***P < 0.005) calculated by 1-way ANOVA. (B) Adiponectin message in CD4+ T cells isolated from blood (open squares), spleen (open diamonds), and graft (crosses) 0, 7, 14, 21, and 28 days after transplantation. Each symbol represents 1 animal in each group. (C) WT CD4+ T cells isolated from both spleen (open diamond) and graft (cross) 4 weeks after transplantation produced adiponectin in response to polyclonal stimulation with bead-conjugated antibodies to CD3 and CD28 for 1 day. Each symbol represents 1 animal in each group, and bars indicate ± SEM.

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