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Biomedical subjects

P Sansoni

Publications and source records attributed to P Sansoni.

At least 55 records · Page 3Linked to original sources

The S-100 beta protein in normal human peripheral blood is uniquely present within a discrete suppressor-T-cell compartment.

The S-100-positive T lymphocytes, and, particularly, the S-100 beta subunit, are restricted, as demonstrated by quantitative subset analysis and double-labeling (gold-peroxidase) immunoelectron microscopy of T-cell subpopulations, to an unique T8-positive cell subset which interestingly was 9.3-negative and CD11b-positive. Since both the T8-positive, 9.3-negative and the T8-positive, CD11b-positive subpopulations have been demonstrated to show suppressive activities, the S-100-positive T cells seem to be closely restricted to a small T-suppressor-cell compartment. Although functional studies on viable isolated S-100 beta-positive cells are impossible to achieve, due to the lack of this protein on the cell membrane, its presence in a discrete T-suppressor compartment might suggest a possible role for the S-100 beta-positive T cells in the regulation of the immune system.

Antigens, Differentiation, T-Lymphocyte↗

Immunoelectronmicroscopic demonstration of S-100 protein in hairy cell leukemia cells.

Hairy cell leukemia (HCL) is generally considered a neoplastic proliferation of B-cell lineage. Among immunocompetent cells, however, S-100 protein is also demonstrated in "dendritic" cells (i.e., interdigitating reticulum cells, Langerhans cells, follicular dendritic cells) and in a small percentage of T8-cells. This study reports the surprising detection of S-100 protein in peripheral blood HCL cells of B-cell type, using immunofluorescence and immunoelectronmicroscopy. However, negative results for S-100 protein staining were obtained in paraffin splenic sections of HCL cases. This report stresses the need for caution in the interpretation of immunocytochemical methods and results, and emphasizes the diagnostic ambiguity of the S-100 protein.

Blood Cells↗

One half of the CD11b+ human peripheral blood T lymphocytes coexpresses the S-100 protein.

The expression of the CD11b antigen and the presence of the S-100 (and, specifically, its beta subunit) protein within the T4- subpopulation of normal human peripheral blood lymphocytes were investigated by panning techniques, immunofluorescence analysis and immunoelectronmicroscopy. Both antigens are known to be absent in the T4+ lymphocytes. However, CD11b+ T lymphocytes represented about 30% of the T4- population; a part of them (over 1/3) belonged to and completely filled up the T4- T8- subpopulation, whereas the remaining part (almost 2/3) shared the T8 positivity. Interestingly, S-100+ T lymphocytes, which always were CD11b+ too, represented about one half of the CD11b+ T cells, but were excluded from the T4- T8- CD11b+ subpopulation, whereas they represented up to 80% of the T4- T8+ CD11b+ subset. Such findings demonstrate that the S-100+ T lymphocytes are exclusively restricted to a discrete T cell compartment which shows the T8+ CD11b+ immunophenotype. Since such T8+ CD11b+ cells had been shown to possess suppressive capabilities, we herein propose that S-100+ lymphocytes might to some extent modulate the immune responses. However, the exact functional significance of the S-100 protein still remains unknown.

Antigens, Differentiation, T-Lymphocyte↗

S-100-positive T cells are largely restricted to a CD8-positive, 9.3-negative subset.

The present report concerns the demonstration of the exclusive detection among peripheral blood T-lymphocytes of the S-100 protein within the CD8-positive subpopulation which lacks the antigen recognized by the 9.3 monoclonal antibody. Highly purified human peripheral blood T-cell subsets, obtained by means of panning techniques, were first stained, by an immunofluorescence method, with purified anti-S-100 protein antibodies. The vast majority of S-100 protein- (and, specifically, its beta subunit) positive cells were detected in the CD8-positive, 9.3-negative subset. This subset had previously been shown to comprise all the alloantigen-specific and histamine-inducible suppressor T-cells. Other T-subsets, even those showing either CD8-positivity (but 9.3-positivity) or 9.3-negativity (but CD8-negativity), were, as a rule, S-100 negative. Immunoelectronmicroscopy confirmed that the S-100-positive cells, showing peroxidase activity within the cytoplasm, were found exclusively within the CD8-positive, 9.3-negative subset. This finding of S-100 protein in cells of a specific T8 suppressor subset extends the range of the known distribution of this protein and may have important implications concerning its role in the modulation of immune responses.

Antibodies, Monoclonal↗

Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes.

Using the radioligand beta-adrenergic blocker [125I]cyanopindolol (ICYP), we have characterized the beta-adrenergic receptors on Leu 3+ (T helper [TH]), Leu 2+, 9.3- (T suppressor [Ts]) and Leu 2+, 9.3+ (T cytolytic [Tc]) subsets of human lymphocytes. Peripheral blood T cells were isolated by rosetting, and then subsets were purified by their affinities to monoclonal antibodies against their Leu 3 and 9.3 markers. ICYP binding to the subsets was saturable with time and with concentration; the binding was stereoselective and reversible by beta-adrenergic antagonists. A biological response produced by beta agonists increased intracellular concentrations of cAMP and corresponded to the number of binding sites. Each subset of cells had a number of binding sites, which was characteristic for the given subset. The data indicate that the density of distribution of beta-adrenergic receptors was not homogeneous on the precursors of phenotypically and functionally distinct T cells (Ts approximately 2900, Tc approximately 1800 and TH approximately 750 binding sites). The displacement studies using beta-adrenergic agonists were performed on the cytolytic and suppressor T cell subsets, suggesting that the receptors were mainly of the beta-2 type. The immunobiological significance of such selective distribution of numbers and subtypes of beta-adrenergic receptors on distinct T cell subsets is under investigation.

Epinephrine↗

Clonal analysis of intrahepatic T lymphocytes in chronic active hepatitis. Isolation of a T-cell line specific for hepatitis B core antigen from a patient with serological evidence of exposure to HBV.

We have evaluated whether peripheral blood and hepatic lymphocytes from a patient with chronic active hepatitis (CAH) and antibodies to HBV in serum were specifically sensitized to HBV envelope antigens (HBsAg and pre-S Ag) or to HBcAg. No proliferation to HBV antigens was demonstrated upon stimulation of peripheral blood mononuclear cells either unfractionated or enriched in CD4+ (helper/inducer) T cells. Of 15 T-cell cloned lines (7 CD8+ and 8 CD4+) obtained by limiting dilution in the presence of PHA and recombinant IL2 from liver-infiltrating lymphocytes, one, designated H2, showed specific sensitization to HBcAg, whereas none demonstrated sensitization to viral envelope antigens. The H2 line displayed the CD8+ phenotype, suppressor activity on polyclonal immunoglobulin production and IL2-dependent, HBcAg-specific proliferation. These results suggest that in patients with CAH and serological evidence of previous exposure to HBV, it is possible to obtain lymphocytes specifically sensitized to HBcAg from liver biopsy.

Adult↗

Natural killer cells expressing the Leu-11 antigen display phagocytic activity for 2-aminoethylisothiouronium bromide hydrobromide- treated sheep red blood cells.

Natural killer (NK) cell subpopulations, identified by anti-Leu-7 and/or anti-Leu-11 monoclonal antibodies, have been investigated in immunoelectron microscopy by using a peroxidase-colloidal gold double labeling system. More than 90% of non-E rosetting/non-adherent Leu-11+ cells and approximately 60% of E rosetting Leu-11+ cells displayed phagocytic capacity for 2-aminoethylisothiouronium bromide hydrobromide treated sheep red blood cells, whereas Leu-7+ -Leu-11- cells consistently failed to ingest 2-aminoethylisothiouronium bromide hydrobromide treated sheep red blood cells. The phagocytic activity of Leu-11+ cells was not dependent on the Leu-7 antigen coexpression. Moreover, the NK capability of Leu-11+ cells has been verified. In both E rosetting and non-E rosetting/non-adherent cell populations, Leu-11+ enriched subsets displayed significantly higher NK capability when compared with Leu-11- cells. Previous reports provided evidence for different cytotoxic capability, recombinant human interleukin 2 mediated activation, and ultrastructural features of Leu-11+ cells in comparison to Leu-7+-Leu-11- cell subset. The data from the present investigation indicate that 2-aminoethylisothiouronium bromide hydrobromide treated sheep red blood cells phagocyting NK cells are confined to the Leu-11+ subset and give added strength to different function capabilities of Leu-11+ and Leu-7+-Leu-11- cells.

Aged↗

Selective sensitization of peripheral blood T lymphocytes to hepatitis B core antigen in patients with chronic active hepatitis type B.

The proliferative response of peripheral blood T cells to hepatitis B surface antigen (HBsAg), pre-S antigen and hepatitis B core antigen (HBcAg) has been studied in 20 patients with hepatitis B virus induced chronic active hepatitis (CAH) and in 12 control subjects. Eleven of the 20 CAH patients showed a significant T lymphocyte proliferative response to HBcAg, whereas no proliferation was detectable in response to envelope antigens (HBs and pre-S) in any patient. T cell subset fractionation revealed that HBcAg specific proliferation was limited to the CD4+ (helper/inducer) population. CD8+ (suppressor/cytotoxic) T cells were unresponsive to HBcAg and did not suppress the proliferative response of autologous CD4+ cells. The HBcAg specific T cell proliferative response did not correlate with serum anti-core antibody titres or with biochemical evidence of liver disease. The present results show the selective presence of HBcAg-sensitized T cells in the peripheral blood of patients with HBsAg positive CAH and suggest that the peripheral lymphoid compartment may not reflect immunopathogenetically important cellular events operative at the site of tissue injury.

Adult↗

Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells.

One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral blood were further separated with antibody 9.3 into Leu 2+, 9.3+, and Leu 2+, 9.3- subsets and each subset was incubated with different concentrations of histamine before determining their ability to suppress immune responses in vitro. The results indicate that the Leu 2+, 9.3- subpopulation includes all histamine-induced suppressor cells, that 10(-4) M histamine is the optimal concentration for suppressor cell induction, and that exposure of Leu 2+, 9.3- cells to histamine for 30 s is sufficient to initiate the induction process. After treatment with histamine these cells inhibit both phytohemagglutinin-induced T cell proliferation and pokeweed mitogen-induced B cell differentiation. The suppression of phytohemagglutinin-induced proliferation was resistant to x-irradiation with 1,200 rad, either before or after histamine exposure, suggesting that Leu 2+, 9.3- cells need not proliferate to become suppressor cells or exert suppression. Moreover, suppression by these cells was not due to altered kinetics of the response. Finally, a histamine type 2 receptor antagonist (cimetidine) but not a type 1 receptor antagonist (mepyramine) blocked the induction of suppressor cells. On the basis of these results and our previous studies of antigen specific suppressor cells, we conclude that Leu 2+ suppressor cells in man are derived from a precursor pool that is phenotypically distinct from cells that can differentiate into cytotoxic T cells.

Antibodies, Monoclonal↗

Pharmacologic effects of autacoids on subsets of T cells. Regulation of expression/function of histamine-2 receptors by a subset of suppressor cells.

Autacoids (principally histamine, beta adrenergic catecholamines, and prostaglandins E and A) have only recently been recognized as substantive moderators of a number of immune functions. If autacoids are to be considered as potential therapeutic immunomodulators, it is necessary to understand their effects on subsets of T cells while they are and are not in contact with each other. This report demonstrates that autacoid receptors are nonrandomly distributed on phenotypically and functionally distinct subsets of human T cells. Each human T cell subset responded to both histamine and isoproterenol, but the dose response curve and maximal efficacy varied widely between the subsets. The suppressor T cells were more responsive to both histamine and isoproterenol than helper/inducer T cells (TH) or cytotoxic T cells (Tc). We found that after mitogenic stimulation the response to histamine, but not isoproterenol, was greatly increased only in TH (Leu 3+) and Tc (Leu 2+, 9.3+) subsets, and that this effect may be regulated by suppressor T cells (Leu 2+, 9.3-). The dramatic rise in cAMP accumulation in response to histamine in mitogen-treated TH and Tc was totally blocked by an H2 antagonist (cimetidine), but not by an H1 antagonist (mepyramine). These findings indicate interdependence of (a) immunologically uncommitted subsets in their response to selected drugs, and (b) control of basal- and autacoid-induced cAMP production, as well as (c) increased qualitative and quantitative selectivity, which is caused by mitogen. If we had performed these experiments only on unseparated cells we would not have observed the remarkable selectivity of autacoid effects on subsets of T cells.

Autacoids↗

T-cell infiltrate in lichen planus. Demonstration of activated lymphocytes using monoclonal antibodies.

Double layer immunocytochemical procedures were performed on fresh frozen serial sections of lichen planus (LP), using three monoclonal antibodies: OKT3 (T-cells) and two anti Ia-like antigens, monoclonal antibodies. Lymphocytes in dermal LP infiltrates were OKT3 positive and Ia-like positive; lymphocytes in the paracortical area of human normal lymph-node were OKT3 positive and Ia-like negative. Unstimulated peripheral blood-OKT3 positive, E-rosette forming cells of normal donors were Ia-like negative, while the same T-cells, when mitogen-stimulated, became Ia-like positive. Therefore, in dermal infiltrates of LP, T-lymphocytes are Ia-like positive cells, representing an antigen-stimulated T-cell population. The in situ presence of activated T-lymphocytes seems to support the hypothesis of an immunological nature of LP.

Antibodies, Monoclonal↗

Hepatocellular transplantation in rats with toxic induced liver failure: results of iso-, allo- and xenografts.

Intrasplenic hepatocytes transplantation was carried out in Wistar-Lewis strain inbred rats, after inducing acute hepatic failure by intravenous injection of Dimethylnitrosamine (DMNA) (30 mg/kg). Iso-, allo-(CDF-Fisher strain) and xenogeneic (New Zealand White rabbit) grafts were performed. Liver cells suspension was obtained by mechanical separation. The results demonstrated the efficacy of iso- and allotransplants, but not of xenogeneic hepatocytes, in improving significantly the survival rate compared to the control group. It is concluded that immunogenicity of liver cells is a factor which must be taken into consideration in hepatocyte transplantation. Moreover the absence of liver cells into the spleen at one week after the transplant seems to suggest that an intact liver cell is not necessary to improve survival.

Animals↗