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The DC ‐ HIL ligand syndecan‐4 is a negative regulator of T‐cell allo‐reactivity responsible for graft‐versus‐host disease
Author(s) -
Chung JinSung,
Tomihari Mizuki,
Tamura Kyoichi,
Kojima Tetsuhito,
Cruz Ponciano D.,
Ariizumi Kiyoshi
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12027
Subject(s) - immunology , t cell , graft versus host disease , haematopoiesis , biology , antigen , transplantation , cytotoxic t cell , stimulation , immune system , stem cell , microbiology and biotechnology , medicine , in vitro , endocrinology , biochemistry
Summary Acute graft‐versus‐host disease ( GVHD ) is the most important cause of mortality after allogeneic haematopoietic stem cell transplantation. Allo‐reactive T cells are the major mediators of GVHD and the process is regulated by positive and negative regulators on antigen‐presenting cells ( APC ). Because the significance of negative regulators in GVHD pathogenesis is not fully understood, and having discovered that syndecan‐4 ( SD ‐4) on effector T cells mediates the inhibitory function of DC ‐ HIL on APC , we proposed that SD ‐4 negatively regulates the T ‐cell response to allo‐stimulation in acute GVHD , using SD ‐4 knockout mice. Although not different from their wild‐type counterparts in responsiveness to anti‐ CD 3 stimulation, SD ‐4 −/− T cells lost the capacity to mediate the inhibitory function of DC ‐ HIL and were hyper‐reactive to allogeneic APC . Moreover, infusion of SD ‐4 −/− T cells into sub‐lethally γ‐irradiated allogeneic mice worsened mortality, with hyper‐proliferation of infused T cells in recipients. Although there my be little or no involvement of regulatory T cells in this model because SD ‐4 deletion had no deleterious effect on T ‐cell‐suppressive activity compared with SD ‐4 +/+ regulatory T cells. We conclude that SD ‐4, as the T ‐cell ligand of DC ‐ HIL , is a potent inhibitor of allo‐reactive T cells responsible for GVHD and a potentially useful target for treating this disease.

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