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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 2

Adiponectin modifies the expression of cytokines by macrophages.

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Adiponectin modifies the expression of cytokines by macrophages.
(A) Cel...
(A) Cells infiltrating cardiac allografts were isolated, and macrophages were identified by expression of CD11b and F4/80 in flow cytometry. The number of CD11b+ and F4/80+ cells per mg of tissue were calculated for allografts to WT (n = 6) and adiponection-KO (n = 5) recipients. (B and C) Isolated infiltrating macrophages expressed increased message for CXCL9, CCL5, CCL2, TLR7, and TLR9 in the adiponectin-KO mice (closed triangles) compared with the WT mice (open circles). Expression of YM-1, Fizz1, IL-10, TGFβ, VEGF, and IL-6 were decreased in the adiponectin-KO mice compared with WT mice. (D and E) Isolated macrophages were cultured for 3 days in the presence of 10 μg/ml recombinant adiponectin (open circles) or absence of adiponectin (closed triangles). In the absence of adiponectin, macrophages maintained increased expression of CXCL9, CCL2, and TLR9. Adiponectin induced an increase in Ym1, TGFβ, Fizz1, IL-10, VEGF, and IL-6. Each symbol represents 1 animal, and bars indicate ± SEM. RT-PCR results are expressed as fold changes normalized to β actin. Significant differences are indicated as ****P < 0.00001, ***P < 0.0001, and **P < 0.005. Student t test nonparametric was performed for A. A 2-way ANOVA was performed with the Bonferroni-Dunn method as a post hoc correction for multiplicity of gene testing for B–E.

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