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Biomedical subjects

W L Olszewski

Publications and source records attributed to W L Olszewski.

At least 91 records · Page 5Linked to original sources

Syngeneic and allogeneic blood transfusions produce hematopoietic and immune effects.

Blood transfusions (BT) should be considered as transplantation of blood elements. They evoke various alterations in the immune responsiveness of blood recipients, contributing to an increased risk of infection and cancer recurrence. The exact mechanism by which blood transfusions induce a state of reduced immune responsiveness remains unclear. Relatively little is also known about immune changes occurring in lymphoid compartments other than blood following blood transfusions. In the present study, the effect of syngeneic and allogeneic blood transfusions on hemopoiesis and immune responsiveness was examined in a rat model. Transfusions of both syngeneic and allogeneic blood caused an increase in the bone marrow myeloid and lymphoid lineage cell compartments as well as a rise in the percentage of OX7+ stem cells in bone marrow. It was followed by a release of OX7+ stem cells into blood circulation, higher in the case of rats transfused with syngeneic blood. The changes in hemopoiesis were accompanied by a diminished responsiveness of blood, spleen and bone marrow lymphocytes to mitogens in both groups of rats. Data point to early changes in distribution and reactivity of bone marrow and lymphoid cells following blood transfusion.

Animals↗

Reconstitution of lymphoid tissue after vascularized bone marrow transplantation.

We reported previously that vascularized bone marrow transplantation (VBMT) in an orthotopic hind limb graft brings about complete repopulation of bone marrow cavities in lethally irradiated syngeneic recipients within 10 days. Intravenous infusion of an equivalent volume of bone marrow cell suspension was evidently less effective. The purpose of this study was to investigate the reconstitution of immunocompetent compartments of lethally irradiated syngeneic rats after VBMT. Lewis rat hind limbs were transplanted orthotopically into irradiated recipients. Ten days after irradiation and bone marrow transplantation, bone marrow, mesenteric lymph nodes and sera from rats were harvested. Responsiveness of mesenteric lymph node lymphocytes (MLNL) to mitogens and lymphocyte proliferation in the presence of sera and bone marrow cell (BMC) culture supernatants was measured. Our studies have shown that vascularized bone marrow transplantation brings about rapid replenishment of lymphoid organs of lethally irradiated syngeneic recipients. The repopulating subsets were fully responsive to mitogens. Sera from reconstituting rats had no evident effect on proliferation of mature lymphocytes. Intravenous infusion of BMC in suspension, in a number equivalent to that grafted in hind limb transplant, was less efficient in reconstituting lymphoid tissue.

Amputation, Surgical↗

Rejection of cartilage formed by transplanted allogeneic chondrocytes: evaluation with monoclonal antibodies.

Cellular infiltrates participating in rejection of cartilage formed by transplanted allogeneic rat epiphyseal chondrocytes were evaluated immunohistochemically using a panel of different monoclonal antibodies. One week after transplantation, the grafts were surrounded by numerous class II MHC+ (OX6+, OX17+), CD4+ (W3/25+), and W3/13+ cells as well as some ED1+ monocytes/macrophages. Only a few T (OX19+) and B (HIS14+) cells were present. The number of class II MHC+ cells and ED1+ monocytes/macrophages did not change significantly in the course of rejection whereas the number of CD4+ and W3/13+ cells gradually decreased. On the other hand, there was a significant increase in the number of CD8+ (OX8+) cells. CD8+ cells accumulated close to the transplants and some of them penetrated cartilage matrix suggesting that they might be involved in chondrocyte killing. After 3 months, cartilage was almost completely destroyed and the intensity of infiltrations was markedly decreased. Fibrous connective tissue predominated, however, some class II+ as well as few ED1+, CD4+ and CD8+ cells were still present adjacent to the cartilage remnants. At the time of transplantation, chondrocytes were endowed with RT1.D class II antigen (OX17+), but they did not react with OX6 mAb (monoclonal antibody) recognizing the RT1.B class II molecule. However, after 1 week, some chondrocytes reacted with OX6 mAb and the number of RT1.B positive chondrocytes increased in the course of cartilage rejection.

Animals↗

Cytokines and adherence molecules involved in spontaneous dendritic cell-lymphocyte clustering in skin afferent lymph.

The skin afferent lymph dendritic cell (DC) spontaneously forms clusters with autologous T cells. The role of adhesion molecules and cytokines in this process was investigated. Analysis of the expression of adhesion receptors on the canine peripheral lymph DC revealed the presence of CD54, CD58, CD18 as well as CD49d and CD49e molecules and cell surface fibronectin. The CD54 and CD58 molecules were found to play a key role in the 'spontaneous' lymph cell clustering. Antibody against fibronectin, a substrate for CD49d and CD49e receptors, reduced DC-lymphocyte binding. Analysis of the effect of cytokines revealed that the pro-inflammatory IL1 beta rather than IL1 alpha, and TNF alpha may be responsible for the enhanced lymph cell in vitro clustering. The IL6 had no such augmenting effect. The enhancing effect of endogenous IL1 beta present in lymph was reduced by the IL1 beta neutralizing antibody. The effect of exogenously added IL1 beta was also limited by the IL1 receptor antagonist. The IL1Ra alone had no effect on cell binding, even when used in the high doses. Neutralizing of IL1Ra in lymph with the specific antibody brought about augmented cluster formation. The enhancing properties of TNF alpha on cell binding were reduced by the TNF alpha neutralizing antibody. The IL10 significantly limited lymph DC cluster formation with T cells. In conclusion, these data demonstrate that the present in lymph IL1 beta and TNF alpha may be responsible for the observed in vitro enhanced cluster formation of lymph DC with autologous T lymphocytes. Cell binding can be reduced by IL1Ra and by IL10. It provides insight into the potential clinical use of these inhibitors.

Animals↗

Liver sinusoidal passenger lymphocytes reveal suppressive properties and prolong allograft survival.

Liver sinusoidal washout cells are low responders to mitogens, and suppressive in autologous PBM, and portal blood mononuclear cells, PHA supplemented, and autologous mixed lymphocyte cultures. They are less immunogenic after IV administration into allogeneic recipients than PBM, which could be measured in an in vivo allogeneic lymphocyte elimination test. The level of immunization is strain dependent. In the BN to LEW combination, they are more immunogenic than in the LEW to DA pairs. This parallels heart allograft survival times, which were longer in LEW to DA than BN to LEW combinations.

Animals↗

Kinetics of distribution of recirculating lymphocytes during whole body hyperthermia.

Whole body hyperthermia (WBH) not only embraces lymphocyte migration to the bone marrow and skin, but also prolongs their subsequent transit through these organs, while inhibiting homing to the lymphoid organs. The effect of WBH is transitory, it subsides within 16 h after a 8 h WBH period. The accumulation of circulating lymphocytes in lymph nodes, Payer's patches and spleen dropped significantly between 4 h and 8 h in WBH, but rose during subsequent 16 h normothermia. In the absence of the adrenal glands, the enhanced bone marrow localization observed in non-adrenalectomised rats during WBH did not occur. Skin localization increased while splenic localization fell in adrenalectomised as compared to non-adrenalectomised rats. These results strongly support the hypothesis that WBH-induced enhancement of lymphocyte migration to the bone marrow is adrenal-hormone dependent. The above mentioned changes can not be attributed to changes in blood flow to the tissues during WBH. Blood flow to the bone marrow was not significantly different from flow to this organ in normothermic rats. Flow to the skin fell significantly and yet localization in this tissue during WBH was higher than during normothermia.

Adrenalectomy↗

Liver sinusoidal washout cells transferred to allogeneic recipients reveal tolerogenic properties.

Liver sinusoidal washout cells, containing a large fraction of LGL cytotoxic to tumor cell lines in vitro, are less responsive to mitogens and suppress the responsiveness of autologous and third-party PBM to mitogens and autologous mixed lymphocyte culture, compared with autologous portal vein or PBM. They are less immunogenic after IV administration into allogeneic recipients, which can be observed in an in vivo allogeneic lymphocyte cytotoxicity test. Immunization of allogeneic recipients with liver sinusoidal washout cells slightly prolongs heart allograft survival time.

Animals↗