Objectives To explore the role of regulatory T (T-reg) cells in the establishment of immune tolerance induced by donor-specific transfusion (DST) in mice with skin-heart transplantation. Methods C57BL/6 mice received DST of splenocytes from CD47(+/+) or CD47(-/-) H-2(bm1) mice or no DST 7 days before skin-heart transplantation from major histocompatibility complex class I-mismatched H-2(bm1) donors. The number and proportion of T-reg cells in graft and lymphoid organs were measured by flow cytometry (FACS) and immunohistochemistry (IHC). The inhibitory function of T-reg cells and anti-donor T-cell responses were assessed by mixed lymphocyte reaction. Results We observed that mean survival time (MST) of skin or heart graft was significantly longer in C57BL/6 mice which received DST from CD47(+/+) H-2(bm1) mice than from CD47(-/-) H-2(bm1) mice. By FACS, we found that the number of T-reg cells in spleen was increased significantly in mice which received CD47(-/-) DST compared to mice which received CD47(+/+) DST. However, the percentages of T-reg cells in total splenocytes and lymph node cells were significantly higher in mice that received CD47(+/+) DST than mice which received CD47(-/-) DST. Immunohistochemistry showed an increased heart grafts infiltration of T-reg cells in the recipients with CD47(-/-) DST, but not CD47(+/+) DST. Supporting this, we found that donor T-cell proliferation was significantly suppressed in mice which received CD47(+/+) DST compared to mice which received CD47(-/-) DST. There was no difference of inhibitory function of T-reg cells between these two groups. Conclusion Our results indicated that CD47 expression on DST cells plays an important role in the induction of immune tolerance in mice with skin-heart transplantation. Increased percentage of T-reg cells may contribute to immune tolerance induced by CD47(+/+) DST.
[1]Jilin Univ, China Japan Union Hosp, Dept Pathol, Changchun, Jilin, Peoples R China.
[2]Jilin Univ, Dept Urol, Hosp 1, Changchun, Jilin, Peoples R China.
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