Characterization of waves of leukocyte recruitment to the lung allograft and the effect of CTLA4-Ig

概要

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MHC-mismatched lung allografts are rapidly rejected by the host immune response. We analyzed cells infiltrating the grafted lung tissue using a collagenase-digestion method. The grafted lung was filled with host-derived leukocytes as early as day 1 post transplantation and the majority of the initial infiltrating cells were granulocytes. This initial influx of granulocytes waned rapidly, followed by a steady increase in lymphocytes, particularly T cells, and then by macrophages. The proportion of CD4+ T cells that express CD25 were increased in the graft the majority of which were activated CD4+ cells. We applied cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)-Ig treatment in combination with donor-specific blood transfusion to the transplantation of lung allograft, which was significantly prolonged by the treatment. To examine the cellular and molecular basis of the inhibition of the graft rejection, we evaluated number and cytokine mRNA expression of the cells infiltrating in the lung allograft using collagenase-digestion method, although we were unable to detect significant effects of the treatment. Taken together, this study demonstrates that single cell suspensions from cellular infiltrates of lung tissue is useful for phenotypical and functional studies on cells infiltrating lung tissue after graft transplantation.