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Inhibition of Alloantigen‐Primed Memory CD4 + and CD8 + T Cells by Hematopoietic Chimerism in Mice
Author(s) -
Lan T.,
Chen J.,
Xia J.,
Wang Y.,
Xie B.,
Wang F.,
Qi Z.
Publication year - 2010
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2010.02412.x
Subject(s) - haematopoiesis , cytotoxic t cell , immunology , hematopoietic cell , cd8 , microbiology and biotechnology , biology , antigen , genetics , stem cell , in vitro
Donor‐reactive memory T cells present a special hurdle in transplantation. Although hematopoietic chimerism is effective for inducing donor‐specific tolerance, the effects on memory T cells are unclear. Here, we induced stable chimerism and tolerance in mice (Tolerance group, n = 6) by donor‐specific transfusion (DST) plus anti‐CD154 monoclonal antibody (mAb), avoiding the toxic myeloablative conditioning treatment to assist bone marrow transplantation (DST/aCD154&BMTx). We then transferred memory CD4 + or CD8 + T cells from donor antigen primed mice to the tolerance‐induced recipients 4 days after heart transplantation (Tol/CD4 + Tm group and Tol/CD8 + Tm group, n = 6, respectively), but neither of these memory T‐cell subsets had an effect on the permanent graft survival (median survival time > 100 days). The unaltered rate of memory T cells in spleen and anergy to donor antigen in vitro demonstrated that these memory T cells were well controlled. The chimerism‐promoting protocol DST/aCD154&BMTx produced an immune environment that included high levels of regulatory T cells (Tregs), microchimerism and TGF‐β, all of which may act in suppressing the donor‐reactive memory CD4 + or CD8 + T cells. These findings have potentially important implications for designing approaches to suppressing memory T cells for success of transplantation.