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Aim: Kaposi's sarcoma (KS) is a lympho-angioproliferative disorder characterized by angiomatous nodules and plaques that mainly affect the skin. The disease is consistently associated with human herpesvirus-8 (HHV8) and with a state of preexistent immunosuppression. Dendritic cells (DCs) have an instrumental role in the activation and function of both innate and adaptative immune responses. At least 2 distinct subsets have been characterized in peripheral blood based on phenotypic markers: myeloid DCs (CD11c+), associated with Ag uptake, T cell activation and ability to secrete IL-12, and plasmacytoid DCs, high virus-induced IFN-alpha producing cells. Because of the role of both DC subtypes in antiviral and antitumor induced responses, we hypothesized that DCs could be involved in the onset and evolution of KS., Methods: Thirty-five patients with mediterranean KS assigned to different clinical stages were compared with 51 healthy control subjects. Peripheral blood DCs were quantified and functionally characterised by flow cytometry directly on whole blood samples. The production of the regulatory cytokines, IL-12 and IL-10, was assessed as intracellular accumulation after incubation with or without lipopolysaccharide (LPS)., Results: Myeloid DCs identified as lineage-/HLA-DR+/CD11c+ cells were significantly lower in KS patients than in controls (0.54+/-0.25 vs 0.69 +/-0.26% of the peripheral blood mononuclear cells; p<0.017). Furthermore, CD11c+ DCs were lower in patients with more diffuse disease. Plasmacytoid DCs, identified as lineage-/HLA-DR+/CD123+ cells, were lower in KS patients (0.23+/-0.19 vs 0.36+/-0.17; p<0.001). DCs from KS patients were more mature, as assessed by expression of the maturation marker CD83, and showed an impaired ability to produce IL-12 upon LPS stimulation, as compared with controls., Conclusion: The numerical and functional alterations of peripheral blood DCs observed in KS patients suggest an involvement of these cells in the onset and evolution of the disease.

In this work we investigated the effects of malnutrition on the immune response in neoplastic patients. We studied the basal NK activity of 34 neoplastic malnourished patients and 10 neoplastic not malnourished patients and a control group of blood donors, by a standard 51 Cr release assay against K562 cells. We observed that the neoplastic malnourished patients have a defective NK activity in spite of a normal number of NK cells, as ascertained by HNK-1 monoclonal antibodies. The reduced NK activity of the neoplastic malnourished patients is only partially restored by rIFN alpha 2a but is normalized by rIL-2 stimulation. We also found that the endogenous IL-2 production from some of these patients is slightly reduced as compared to controls. On the contrary, there are no significative differences between the neoplastic not malnourished patients and blood donors, as concerns the NK activity. These results suggest that nutritional status plays a very important role in the maintenance of an efficient immune response in neoplastic patients.

The "F1 hybrid transplantation law" states that F1 hybrids of two unrelated inbred strains of mice accept grafts from either parent strain while neither parent accept grafts from the F1 hybrid. However, there are two notable exceptions to this law. Indeed, parent grafts containing immunologically competent cells (spleen cells, bone marrow etc.) react against the F1 normal hosts in which they are placed. In the absence of a host-versus-graft reaction, the graft-versus-host reaction (GvH) may dominate the field and cause untoward reactions which not only negate any benefit derived from the graft, but also cause significant, and often fatal morbidity of the host, that is, a GvH Disease (GvHD). Furthermore, irradiated F1 mice are refractory to the grafting of parental bone marrow, lymphoma cells and normal lymphocytes because of a restriction by non-co-dominant, besides that of codominant MHC-H2 genes. These non-co-dominant genes have been designated Hh genes for Hybrid histocompatibility and the phenomenon itself, hybrid resistance. The cellular, humoral and genetic mechanisms involved in the GvH and hybrid resistance production are explained and discussed in the first, while in the second section of the present review, their equivalent in three human pathological situations are taken into consideration. We focus in detail on two principal immunologic aspects of human bone marrow transplantation: GvH and hematopoietic engraftment; each one of these immunologic aspects has considerable impact on the course and outcome of marrow transplantation in humans. The allograft implantation between HLA-genetically-identical siblings, HLA-aploidentical family members or HLA-phenotypically identical donor-recipient couples are herewith examined, while the autologous bone marrow rescue approach is not taken into consideration. The outcome of bone marrow transplantation depends not only on the degree of genetic disparity between the donor and the recipient, but also on the underlying disease. Bone marrow transplantation is the therapy of choice for patients with aplastic anemia, severe combined immunodeficiency (SCID) and other genetic and acquired immunodeficiency, some leukemias and a few other diseases, mainly if HLA-genetically-identical siblings are available. However, in many cases such siblings are not available. Therefore, the probability of acute or chronic GvHD or graft rejection increases significantly. The clinical and pathologic manifestations, the prognostic factors, and the treatment and prevention of acute and chronic GvHD are illustrated in detail.(ABSTRACT TRUNCATED AT 400 WORDS)

In the present study we investigated the role of monocytes and of their soluble products (prostaglandins and hydrogen peroxide) in the modulation of the immune response in 50 untreated patients with Hodgkin's disease (HD) compared with a group of healthy donors. The primary response in vitro has been studied with the method of haemolytic colonies in soft agar. A defective in vitro antibody production has been observed in HD patients. Both Indomethacin addition (10(-6) M, final concentration) and depletion of plastic adherent cells, slightly increased the number of haemolytic areas in cultures from HD patients as compared with healthy donors. Similarly, the addition of catalase (8000 U/ml) which destroys H2O2, that is the main mediator of monocytes suppressor activity in normal subjects, did not restore the response of peripheral blood mononuclear cells (PBMC) from HD patients. These results suggest that monocytic cells play a minor role, if any, in the depression of the immune response in HD patients.

Cellular cAMP was determined by the competitive protein binding assay (RIA method) in peripheral blood lymphocytes (PBL) isolated from 34 healthy blood donors and 31 tumor bearing patients. cAMP concentration in PBL from the cancerous patients was lower than the one found in healthy blood donors. Results are discussed in relation to the modification of immune reactivity induced by cancer.

This work analyses the presence of terminal deoxynucleotidyl transferase (TdT) in neoplastic lymphoid cells from a series of malignant lymphomas and in leukemic cells from blood or bone marrow of patients with lymphoproliferative diseases. The studied cases were 63 patients with acute leukemias, 26 patients with chronic leukemias, 85 patients with lymphomas and 14 normal controls. The presence of TdT in the neoplastic cells was determined by optimized assays of enzymatic activity or by immunofluorescence test for TdT positive blasts. The fluorescence tests made use of anti-TdT antibodies specifically absorbed on cells containing the enzyme and then revealed by a second fluorescent antibody. Appreciable amounts of TdT were found in the white cells of blood or bone marrow from the following 25 out of 35 acute lymphoblastic leukemias (ALL) with modulations in the different phenotypes; 13 out of 14 acute undifferentiated leukemias (AUL); and 9 out of 15 blastic crises in chronic myelogenous leukemia (CMLbc). The enzyme was present in 12 out of 14 lymphomas of lymphoblastic type (LL); 2 B lymphoblastic lymphomas did not show any TdT positivity. The highest levels of TdT were detected in cells classified as immature lymphoblast or in their precursors. TdT was absent from normal lymph nodes from leukocytes of chronic lymphocytic leukemia (CLL) and chronic (CML) and acute myelogenous leukemia (AML). 2 out of 14 cases of AML showed a border-line positivity. A definite correlation between concentrations of enzymatic activity and percentage of immunofluorescent cells could not be established. We did not find a precise correlation between the TdT content of lymphoid blasts and other clinical prognostic indices.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-three malignant melanoma patients were tested for NK cytotoxicity of peripheral blood lymphocytes in a Cr-release assay. NK activity was significantly lower in patients as compared with controls. In eight patients no cytotoxicity whatsoever could be detected. We tried to understand this NK impairment by using further assays such as the removal of plastic adherent cells or of carbonyl-iron phagocytizing cells and by mixing experiments. Only three patients showed the presence of NK activity suppressing cells and one patient had suppressive factors in his serum. No correlation was seen between NK activity values and clinical-biological parameters such as thickness of tumor, stage of disease, rate of recurrences or hystological findings.