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Donor double‐negative Treg promote allogeneic mixed chimerism and tolerance
Author(s) -
He Kathy M.,
Ma Yuexia,
Wang Shuang,
Min WeiPing,
Zhong Robert,
Jevnikar Anthony,
Zhang ZhuXu
Publication year - 2007
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200737408
Subject(s) - immunology , biology , cd8 , perforin , transplantation , immune tolerance , adoptive cell transfer , major histocompatibility complex , transplantation chimera , t cell , immune system , medicine , microbiology and biotechnology , stem cell , haematopoiesis , hematopoietic cell , surgery
Abstract Bone marrow (BM) transplantation is an efficient approach to develop donor‐specific tolerance and prevent chronic rejection. Allogeneic BM transplantation is limited by donor T cell‐mediated graft‐ versus ‐host disease, requirement of cytoreduction and high numbers of BM cells. In addition of these drawbacks, recent studies demonstrate that not only T cells, but also NK cells can mediate BM rejection, and long‐term mixed chimerism depends on NK cell tolerance. Thus, NK cell is another potential barrier against engraftment of BM and an important target in efforts to induce transplant tolerance. We have previously identified a novel type of Treg with the phenotype TCRαβ + CD3 + CD4 – CD8 – (double‐negative, DN). We and others have demonstrated that DN‐Treg can effectively suppress anti‐donor T cell responses. In this study, we found that donor‐derived DN‐Treg can suppress NK cell‐mediated allogeneic BM graft rejection in both parent‐to‐F1 and fully MHC‐mismatched BM transplantation models. Perforin and FasL in DN‐Treg play important roles in the suppression of NK cells. Furthermore, adoptive transfer of DN‐Treg can promote a stable mixed chimerism and donor‐specific tolerance without inducing graft‐ versus ‐host disease. These results demonstrate a potential approach to control innate immune responses and promote allogeneic BM engraftment.