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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 6

T cell secretion of adiponectin is induced by specific antigen.

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T cell secretion of adiponectin is induced by specific antigen.
(A) Tota...
(A) Total leukocytes and CD4+ T cells isolated from spleen and grafts were tested in an ELISPOT assay to determine the frequency of cells producing adiponectin. (B) Adiponectin protein measured by ELISA in tissue homogenates from allografts to RAG-/- mice that were reconstituted with either 2 × 104 naive CD4+ T cells (nCD4), 1 × 103 Marilyn cells, or 2 × 104 Marilyn cells (n = 4). (C) Immunohistology for CD3+ cells in allografts to RAG-/- mice that were reconstituted with 1 × 103 Marilyn cells or (D) 2 × 104 Marilyn cells. (Scale bar = 50 μm). Significant differences are indicated as ****P < 0.00001 and ***P < 0.0001 by 2-way ANOVA. Bars indicate ± SEM.

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