XENOGRAFT REJECTION OF PORCINE ISLET-LIKE CELL CLUSTERS IN NORMAL ANDNATURAL-KILLER CELL-DEPLETED MICE

Fetal porcine islet-like cell clusters (ICC) were transplanted under t he renal capsule of normoglycemic normal or athymic (nu/nu) C57BL/6 mi ce, Control animals were implanted with allogeneic minced kidney tissu e from C57BL/Ks mice, The animals were killed 6 or 14 days after trans plantation and the grafts were processed for flow cytometric analyses or immunohistochemistry, Xenograft destruction was evident in normal m ice on day 6 after transplantation. The majority of infiltrating cells were macrophage-like cells expressing the F4/80 antigen, Lymphocytes expressing the CD3 antigen were in minority and mainly located in the peripheral parts of the ICC xenograft, The frequency and distribution of CD4(+) cells were found to resemble those of the CD3(+) cells, A la rge number of infiltrating cells, including several macrophage-like ce lls, expressed the Thy 1.2 antigen, Flow cytometry of infiltrating cel ls in the ICC xenograft revealed that approximately half of the cells expressing the F4/80 antigen also expressed Thy 1.2 and/or CD4. No cel ls were found expressing both the F4/80 and CD8 antigens, Both the F4/ 80 single-positive and the F4/80, CD4 double-positive cells were found to be larger and more granular than the CD4 single-positive cells, No co-expression of CD4 or Thy 1.2 with the F4/80 antigen was detected o n cells infiltrating allogeneic tissue grafts, Moreover, a relative la rge number of cells (approximate to 15%) in the xenograft expressed th e NK 1.1 antigen as determined by flow cytometry, The role of natural killer (NK) cells in islet xenograft rejection was further evaluated i n mice depleted of NK cells, using intraperitoneal injections of the m onoclonal antibody NK 1.1. The simultaneous inoculation and subsequent growth of the NK cell-sensitive beta(2)-microglobulin-deficient mutan t, C4.4-25(-), lymphoma cell line EL-4 served as an in vivo control of Nh cell depletion, However, all NK cell-depleted mice rejected the IC C xenograft. In contrast, athymic mice permanently accepted the porcin e ICC xenograft but, readily rejected the NK cell-sensitive lymphoma c ell line. Taken together, ICC xenograft rejection in mice seems to be T cell dependent, as evidenced in the nude mice model, while the main effector cell appears to be a macrophage with a unique phenotype.