Liver sinusoidal blood containing natural killer-like cells.

Rat liver sinusoidal washout cells were examined. These cells, which are marginated in sinusoids, could be washed out by simple flushing of the vasculature with culture media without enzymes and under physiological portal pressure. They revealed, in comparison to peripheral blood mononuclear cells, high cytotoxic activity commonly attributed to the natural killer (NK) and natural cytotoxic (NC) cells, and were found to be anti-asialo-GM1-negative. Liver sinusoidal cytotoxic cell (LSCC) activity has been found to be associated with the large granular lymphocytes in low-density cells in OX8-positive as well as in OX8-negative populations. The mononuclear cells washed out from the liver microvasculature could be stimulated with NK-sensitive targets to release soluble factors which selectively lyse YAC-1 tumour cells and inhibit growth of normal haematopoietic granulocyte-macrophage colony-forming cells in vitro. The cytotoxic cell population in the liver turned out to be blood-borne in origin and not resident. Our findings suggest that liver sinusoidal cytotoxic cells represent an NK population with a predilection for marginating in the liver and may be important in eliminating tumour or virus infected cells passing through the liver from the circulation. The mechanism of their accumulation in liver sinusoids remains unclear.

Prolongation of heart graft survival and spleen suppressor cell activity after donor specific blood transfusions in rats differing across the MHC.

The aim of the study was the prolongation of heart allograft survival in rats after DST (donor specific blood transfusion), the characterization of T and B lymphocyte phenotypes in peripheral blood, spleen and lymph nodes and the evaluation of specific and nonspecific suppressor cell activity of spleen and blood lymphocytes of DST rats. Pretreatment of Wistar recipients with one, two and three doses of DST-s prolonged the heterotopic August graft survival to 11.0, 12.3 and 11.4 days, respectively (rats differed across the MHC). Spleen lymphocytes of transfused rats showed significant nonspecific suppressive activity in culture with syngeneic spleen lymphocytes of nontransfused rats stimulated with PHA, but not in culture with blood lymphocytes. Blood lymphocytes of transfused rats did not show any nonspecific suppressive activity. Spleen and blood lymphocytes of transfused rats did not demonstrate any specific suppressive activity in allogeneic MLC. The ratio of W3/25+/OX8+ (Th+/Tsup/cyt+) cells in peripheral blood was found increased in DST rats due to the decrease in the percentage of OX8+ cells whereas the opposite effect was observed with spleen cells (increase in the percentage of OX8+ cells after one DST). The number of OX6+ (Ia positive) cells and B cells in all transfused rats was found unchanged comparing with untreated animals.

Prolongation of heart allograft survival in course of donor specific antigen and alloserum treatment in the rat.

Different cell subpopulations involved in the induction of immune enhancement of the heart graft survival in rats differing across the major histocompatibility barrier has been studied. Cells devoid of class II antigens on their surface, e.g. erythrocytes, platelets, and thymocytes have been found ineffective, whereas subpopulations rich in class II antigens were found to be highly effective in induction of specific unresponsiveness when combined with donor specific alloserum. Our results suggest that class II antigens take part not only in induction of rejection response but may be also responsible for generation of specific unresponsiveness towards donor antigens.

Synergistic effects of ATS and passive and active enhancement on heart and skin allografts in rats.

The effect of a combination of specific and non-specific immunosuppression on survival of heart and skin allografts in parental strain rats differing across the major histocompatibility locus was investigated. Pretreatment of the recipient with donor specific antigen and anti-donor alloantiserum prolonged the survival of heart grafts but not skin grafts. The use of antilymphocyte serum prolonged skin graft survival but not heart graft survival. However, when ATS was combined with donor specific immunosuppression, both heart and skin graft survival were prolonged dramatically. It is suggested that these treatment modalities affect differentially various aspects of the immune responses.

Hepatic lesions in dogs treated with horse antidog lymphocyte globulin (HADLG) after kidney transplantation.

Microscopical examination of the liver of dogs which after allogenic kidney transplantation were transiently treated with antilymphocyte globulin revealed infiltrates of mononuclear cells (lymphocytes, plasma and reticulum cells). These infiltrates were usually situated in perivascular spaces (around the central veins or on the portobiliary tract). A proportion of capillaries showed endothelial proliferation and the narrowing of their lumen. The authors were unable to determine whether these lesions resulted from the direct toxic effect of antilymphocyte globulin or represented a nonspecific reaction to the used preparation.

Enhancement of cardiac allografts in rats at the major AbG locus. I. Synergistic effect of specific and non-specific immunosuppression.

Investigations of the specific and nonspecific immunosupression of heart transplants in rats are presented. Pretreatment of the Wistar recipient of the August heart with donor strain cellular antigen and anti-donor hyperimmune serum 11 and 10 days before transplantation caused enhancement of the heart graft in this strain combination differing in the major AgB histocompatibility locus. Combination of that protocol with non-specific immunosuppression, i.e. ATS treatment caused synergistic effect. Heart grafts in animal treated with that full protocol of biological immunosuppression survived for 50.8 days.

Active enhancement of dog kidney allografts using ALG and donor platelets.

The results of the studies indicate that platelets can be used as donor specific antigen in protocols of "biological suppression". Administration of donor specific platelets 10 days after transplantation to unmatched mongrel dogs treated for a brief period with ALG resulted in a marked prolongation of kidney allograft survival. Acute rejection of a second kidney from an indifferent donor suggests that a state of specific unresponsiveness was achieved by recipients pretreatment with ALG and donor antigen challenge.