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Adoptive transfer of double negative T regulatory cells induces B‐cell death in vivo and alters rejection pattern of rat‐to‐mouse heart transplantation
Author(s) -
Ma Yuexia,
He Kathy M.,
Garcia Bertha,
Min Weiping,
Jevnikar Anthony,
Zhang ZhuXu
Publication year - 2008
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2008.00444.x
Subject(s) - xenotransplantation , adoptive cell transfer , perforin , immunology , cd8 , transplantation , immune system , t cell , biology , in vivo , medicine , microbiology and biotechnology
Background: Antibody‐mediated hyperacute and acute graft rejection are major obstacles in achieving long‐term graft survival in xenotransplantation. It is well documented that regulatory T (Treg) cells play a very important role in regulating immune responses to self and non‐self antigens. Our previous studies have shown that TCRαβ + CD3 + CD4 − CD8 − (double negative, DN)‐Treg cells can suppress anti‐donor T‐cell responses and prolong graft survival in allo‐ and xenotransplantation models. We have demonstrated that DN‐Treg cells can induce B‐cell apoptosis in vitro through a perforin‐dependent pathway. Methods: B6 mice received rat heart grafts, followed by 14 days of LF15‐0195 treatment. Some mice received Lewis rat cell activated DN‐Treg cells after LF treatment. DN‐Treg cells, purified from perforin −/− mice and from B6 mice pre‐immunized with third party rat cells, were used as controls. Results: In this study, we investigated the possibility that adoptive transfer of xenoreactive DN‐Treg cells could suppress B cells in vivo , thus prolonging xenograft survival. We found that apoptotic death of B cells significantly increased after adoptive transfer of DN‐Treg cells. In addition, anti‐donor IgG subtypes were significantly inhibited in the DN‐Treg cell‐treated group, in which the rejection pattern was altered towards cellular‐mediated rejection rather than antibody‐mediated acute vascular rejection. However, perforin‐deficient DN‐Treg cells failed to induce B‐cell death and to prolong heart graft survival, indicating a perforin‐dependent mechanism contributes to B‐cell death in vivo. Conclusions: This study suggests that adoptive transfer of xenoreactive DN‐Treg cells can inhibit B‐cell responses in vivo. DN‐Treg cells may be valuable in controlling B‐cell responses in xenotransplantation.