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Biomedical subjects

M Piantelli

Publications and source records attributed to M Piantelli.

At least 91 records · Page 5Linked to original sources
PubMed1985

Ultrastructural analysis of peripheral blood mononuclear cells in renal allograft recipients.

Renal transplanted patients receiving immunosuppressive therapy with glucocorticoids (GC) and azathioprine show in the peripheral blood numerous large mononuclear cells. The origin and the lineage of these cells was not clearly established. In the present study we investigated the surface phenotype and the ultrastructural characteristics of this subset constituted by large mononuclear cells. From peripheral blood mononuclear cells (PBL) of allograft recipients, a cell preparation exhaustively depleted of the relatively numerous monocytes was obtained. At ultrastructural examination two main cellular populations were distinguished: the predominant one (congruent to 85%) was constituted by cells with lymphoid morphology while the other (congruent to 15%) showed myeloid appearance. The large lymphoid cells, T4 or T8 positive, did not express Ia molecules on the surface and were morphologically suggestive of cells in an intermediate stage of the cell cycle between resting and activated lymphocytes. The myeloid population was constituted by promyelocytes, myelocytes and metamyelocytes. Promyelocytes and myelocytes capable of cell division are responsible for the increase of 3H-thymidine incorporation observed in transplanted patient PBL. In conclusion our data suggest that in allograft recipients the immunosuppressive therapy with GC and azathioprine may inhibit the lymphocyte blast transformation and can influence the release of immature myeloid cells responsible for the PBL increased 3H-thymidine incorporation.

Antibodies, Monoclonal↗
PubMed1984

Ia- and IgG-Fc receptor-positive accessory cell sustains peripheral T lymphocyte but not thymocyte mitogenesis induced by OKT3 monoclonal antibody.

The proliferative responses of human peripheral blood mononuclear cells (PBL) and thymocytes to OKT3 monoclonal antibody have been investigated. The PBL response to OKT3 was maximal after 72 hr while that of thymocytes was inappreciable at all times measured. Unlike phytohemagglutinin, OKT3 was unable to elicit the mitogenesis of adherent cell-depleted T cells in spite of the presence of exogenously added Interleukin 1 and/or Interleukin 2. The addition of autologous or heterologous adherent cells restored the OKT3 mitogenic response of peripheral purified T cells but not of thymocyte cultures. The adherent cell population that was able to sustain the OKT3-elicited T-cell mitogenesis was constituted by Ia-, Fc receptor-positive cells. These data suggest that the adherent cell-T cell interaction is mediated via the Fc portion of the OKT3 molecule. Furthermore, unlike peripheral T cells, T3-positive thymocytes, which represent the more mature. PHA-responsive subset within the thymus, are unable to cooperate with accessory cells when pulsed with OKT3 monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1984

Glucocorticoid inhibitory action on the response to PHA of residual circulatory lymphocytes in renal transplant patients following immunosuppressive therapy.

The inhibitory effect of glucocorticoids on the in vitro response to phytohaemagglutinin of the residual circulating T lymphocytes in renal transplant patients during maintenance immunosuppressive therapy with glucocorticosteroids and azathioprine has been investigated. As in normal subjects, the steroid-induced inhibition of transplanted patients' lymphocyte response was inversely correlated with the mitogen concentration used. On the other hand, the response of the various lymphocyte preparations from transplanted patients appeared less inhibited by steroids than the corresponding preparations from normal subjects. The addition to the culture of the adherent cell product interleukin 1 was effective in removing to a similar extent the steroid inhibitory effect on lymphocytes from normal and transplanted subjects. Thus, the lesser inhibitory effect of glucocorticoids on transplanted patient lymphocytes could be explained by the higher percentages of monocytes present in all peripheral blood mononuclear cell preparations. These results suggest that during immunosuppressive therapy with glucocorticoids and azathioprine the residual circulating lymphocytes have a responsiveness to in vitro dexamethasone suppression similar to that of normal peripheral blood lymphocytes.

Antibodies, Monoclonal↗
PubMed1983

Modulation of glucocorticoid inhibitory action on human lymphocyte mitogenesis: dependence on mitogen concentration and T-cell maturity.

The inhibitory effect of glucocorticoids on the mitogenesis of human T cells derived from thymus and peripheral blood compartments have been investigated. The capacity of dexamethasone (Dex) (10(-7) M) of inhibiting the peripheral blood lymphocyte (PBL) mitogenesis was inversely correlated with the phytohemagglutinin (PHA) concentration used. Conversely, Dex completely (greater than 90%) inhibited the thymocyte mitogenesis, irrespective of PHA concentrations. T cells purified from PBL (M phi less than or equal to 1%) behaved as thymocytes regarding the Dex inhibitory pattern. The addition of macrophages (M phi) or interleukin 1 (IL1) was effective in removing the Dex inhibitory effect on T cells purified from PBL, but not on thymocytes. The higher corticosensitivity of thymocyte mitogenesis in comparison to PBL mitogenesis cannot be explained by differences in the relative number of M phi, but seems an intrinsic property of these less mature T cells.

Cell Survival↗
PubMed1983

Glucocorticoid receptors and cortico-sensitivity in a human clonal monocytic cell line, CM-SM.

CM-SM is a clonal line of human precursor mononuclear phagocytes inducible to macrophage differentiation in response to the tumor promoter phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Untreated CM-SM cells contain single class, high-affinity (KD = 4.0 X 10(-9) M) glucocorticoid-specific receptor sites (approximately 60,000 per cell), as measured by a whole cell assay, at 37 degrees C, using [3H]triamcinolone acetonide (TA). Exposure of CM-SM to dexamethasone (DEX) produced a progressive, dose- and time-related series of changes in CM-SM cell growth, saturation density, morphology, and functional properties, with half-maximal effects at about 10(-9) M for DEX. TA-receptor sites rapidly decreased (about 70%) after DEX treatment, without any apparent change in steroid specificity and affinity. After 5 days in culture with a saturating concentration (3.6 X 10(-8) M) of hormone, the cells reached a saturation density of about 9.0 X 10(6) viable cells/ml (about 4.0 X 10(6) viable cells/ml in the controls), while the modal volume of the resulting cell population was approximately 60%, as compared to the volume of untreated cells. DEX-treated cells appeared less differentiated than controls, as assessed by combined morphologic, antigenic, and cytoenzymatic analyses. DEX almost completely inhibited TPA activation of the following macrophage functions: adherency to the culture plate, expression of lysosomal enzymes, Fc and C3 receptors, and stimulation of phagocytosis. After removal of DEX, the cells, within a few passages, returned to a state apparently identical to the untreated controls and could be induced to macrophage differentiation in response to TPA.

Cell Differentiation↗
PubMed1983

Constitutive production of Interleukin-1 by the human continuous cell line, CM-S.

Supernatants from the human continuous cell line, CM-S, have been tested for Interleukin-1 (IL-1) activity and found to constitutively elaborate this factor. The CM-S-produced IL-1 activity has been partially purified and shown to be similar to IL-1 produced by human and mouse peripheral blood macrophages. To the best of our knowledge this is the first continuous human cell line reported that produces this monokine.

Cell Line↗
PubMed1983

Dissociation between coupled lymphocyte phenotypic and functional properties in Sézary cells.

Neoplastic lymphocytes derived from three patients suffering from Sézary syndrome were studied by immunologic and functional analysis. Populations of neoplastic T cells (greater than 90% as judged by morphologic criteria) were isolated from involved lymph nodes. Sézary cells expressed T3 and T4 but not T8 membrane antigens displaying the same phenotypic pattern of normal helper/inducer T cells. On the contrary the mitogenic response of Sézary cells to phytohemagglutinin appears lower than that exhibited by peripheral T lymphocytes. The amounts of interleukin 2 produced by Sézary cells were examined in two out of three cases: in one case it appeared similar to that produced by peripheral blood lymphocytes while in the other it was about one-half lower. Furthermore the capacity of dexamethasone at 10(-7) M in inhibiting T-cell mitogenesis was comparatively analyzed in T lymphocytes from Sézary lymph nodes, reactive lymph nodes, normal peripheral blood, and normal thymus. It was clearly apparent that the mitogenesis of Sézary cells, unlike that of peripheral blood lymphocytes and that of lymphocytes from reactive lymph nodes, was strongly inhibited by dexamethasone (greater than 70%); such inhibition was very similar to that observed for normal thymocytes. Taken together these results suggest that despite the phenotypic pattern of mature helper/inducer T cells, Sézary lymphocytes are functionally a less mature T-cell type.

Antigens, Surface↗
PubMed1983

A human thymoma with prothymocyte-like infiltration.

We have examined a human thymoma, round-oval epithelial-type cell with moderate lymphocytic infiltration, whose major lymphocytic component (67%), unlike the minor one (33%), did not form rosettes with sheep red blood cells (E rosettes). However, these cells were of T-cell nature as indicated by the positive staining for both acid phosphatase and beta-glucuronidase, two well-accepted cytochemical markers for T cells. The non-E-rosetting lymphocytes expressed T 10, but not T 3 and T 6 antigens. Moreover, they lacked both peanut agglutinin and Fc-IgG receptors. On the contrary, 71 and 19% of the E-rosetting cells were PNA- and Fc-IgM-receptor positive, respectively. Furthermore, the non-E-rosetting cells were phytohemagglutinin unresponsive. The non-E-rosetting lymphocytes were larger (greater than 7 micron) than the E-rosetting cells and showed a different nuclear chromatin pattern. These immunological, cytochemical, and morphological features strikingly resemble those exhibited by cells (prothymocytes) normally found only in fetal thymus. On the basis of these findings we hypothesize the existence in this thymoma of a prothymocyte-like infiltration.

Acid Phosphatase↗
PubMed1983

Human thymoma lymphocyte mitogenesis: glucocorticoid inhibitory capacity as a function of the size of the more mature T cell subset.

The relationship between the expression of T3 and T6 antigens and the capacity to respond to phytohaemagglutinin (PHA) has been studied in the lymphocyte component of nine human thymomas. It appears that there is a positive correlation between the mitogen responsiveness of thymoma lymphocytes and the relative proportion of T3 positive (T3+), T6 negative (T6-), peanut receptor negative and IgM-Fc receptor positive cells. Moreover we have comparatively investigated the dexamethasone (Dex) inhibitory effect on the mitogenesis of T lymphocytes from thymoma, normal thymus and peripheral blood. In the presence of the macrophage product interleukin 1, the capacity of Dex to inhibit the mitogenesis of peripheral blood purified T cells (PBT) is inversely correlated with the PHA concentration used. Conversely, Dex completely (greater than 90%) inhibits thymocyte mitogenesis irrespective of PHA concentration. The entity of Dex inhibitory effect on thymoma lymphocyte mitogenesis shows a great variability ranging between that observed in normal thymocytes and that observed in PBT. In each thymoma case the degree of inhibition appears to be dependent on the size of the more mature thymocyte pool being positively correlated with the number of T6+ but negatively with that of T3+ cells. Our data demonstrate a high degree of variability among thymomas relative to the phenotypic and functional properties of their lymphocytic component. On the other hand, in some thymomas the phenotypic and functional characteristics of lymphocyte component seem to represent only a narrow span of normal thymocyte maturative pathway. In this respect, human thymoma may constitute a profitable tool for studying the intrathymic T lymphocyte maturative steps.

Adult↗
PubMed1982

Functional properties of human thymoma lymphocytes: role of subcellular factors in blastic activation.

The proliferative responses to phytohemagglutinin and the role of subcellular factors in the modulation of blastogenesis of thymoma lymphocytes from 5 thymoma patients were investigated. The addition of exogenous interleukin 1, a macrophage product, strongly augmented the blastic transformation of cultured thymocytes from both normal and neoplastic glands by influencing the production of interleukin 2 (IL-2) by a well-defined T-cell subset. The magnitudes of the blastic responses were ultimately modulated by the amount of IL-2 released in culture. The higher proliferative responses exhibited by thymocytes from thymoma were effectively sustained by a higher production of IL-2 in culture. In addition to having distinctive surface membrane receptors in common with normal thymocytes, thymoma lymphocytes were also under the influence of the same subcellular factors involved in T-cell blastic activation as thymocytes. These observations imply the presence of functionally distinct subpopulations in the thymoma lymphocyte component and add arguments in favor of their nonneoplastic nature.

Adult↗
PubMed1981

Pseudolymphoma of the lung: lymphoid subsets in the lung mass and in peripheral blood.

Studies of the lymphocyte markers in a case of pseudolymphoma of the lung indicate a non-neoplastic nature of the lymphoid infiltrate. The relative proportions of T and B cells and of the markers for the various subsets of both populations reflect the morphologically mixed character of the cellular infiltrate of the lung mass. Moreover, an imbalance of T cell subsets was observed in the peripheral blood: the numbers of T cells with receptors for IgM (TM) were persistently decreased while an increase of the values of T lymphocytes with receptors for IgG (TG) was noted. In addition an altered immunologic status of the patient was indicated by the in vivo impairment of cellular immunity as demonstrated by the failure to respond to common antigens and to become sensitized to 1-chloro-2,4-dinitrobenzene (DNBC).

Adult↗
PubMed1981

Human thymoma: immunologic characteristics of the lymphocytic component.

Several immunologic parameters were investigated in the lymphocytic component of ten thymomas, characterized by a variable degree of lymphocytic infiltration. The majority of thymoma lymphocytes are T-cell in nature, as are lymphocytes from the normal thymus. Lymphocytes from six thymomas with moderate or predominant lymphocytic infiltrates were capable of forming stable E-rosettes, (mean percentage +/- SD: 78.0 +/- 5.2); binding peanut agglutinin (67.3 +/- 8.6); and exhibiting receptors for the Fc-portion of IgM (21.8 +/- 6.0) at percentages that were close to those found in the normal thymus. On the other hand, lower numbers of stable E-rosetting cells (26.8 +/- 8.7), PNA-positive cells (27.5 +/- 12.4), and remarkably higher percentages of cells with receptors for IgM (54.0 +/- 4.2) were demonstrated by the lymphocytic population of four thymomas with scant lymphocyte components. In addition, lymphocytes from tumors with scant lymphocyte components show a higher proliferative response to phytomitogen (PHA), therefore exhibiting immunologic features comparable to those of the more mature pool of normal medullary thymocytes. The observed immunologic similarities between the populations of lymphocytes from thymomas and from the normal thymus gland suggest an exclusively epithelial origin of the thymoma.

Adult↗
PubMed1981

Lymphocyte subsets in human thymus: expression of IgM-Fc receptor by peanut agglutinin positive and negative thymocytes.

The number of cells bearing receptors for the Fc portion of IgM (TM) and IgG (TG) has been evaluated in the human thymus. After overnight incubation the TM cells were 26.2 +/- 2.1% (mean +/- SE) in unfractionated thymus cell suspension, 23.4 +/- 3.8% in peanut agglutinin positive (PNA+) and 32.6 +/- 3.2% in PNA-negative (PNA-) fraction. PNA+ and PNA- fractions mainly consist of cortical and medullary thymocytes, respectively. The presence of TG was negligible. The fine structural features of TM cells from the thymus were very similar to those reported for TM lymphocytes from peripheral blood. In short-term culture a time-dependent increase of TM cells was observed. After 96 h of culture more than 60% of the thymocytes were shown to bear the Fc receptor of IgM. At the same time PNA+ and PNA- fractions expressed about 70% and 42% of TM cells respectively. The number of TG remained negligible. Our data indicate that in the human thymus there exists a distinct, quantitatively well-represented TM subset. Most probably, the peripheral TM cells derive from this subset which is present in both the cortex and the medulla of the thymus. Finally, the higher blastic responses to PHA exhibited by TM cells from PNA-subpopulation suggest that the most advanced intrathymic maturative step is attained by this distinct subset.

Agglutinins↗
PubMed1981

Glucocorticoid receptors and in vitro corticosensitivity of peanut-positive and peanut-negative human thymocyte subpopulations.

In 6 human thymus glands, the immature subset of thymocytes was separated from the more mature one, by differential peanut lectin agglutination. These 2 cell subpopulations were analyzed for glucocorticoid receptor content by using a whole cell assay, with (3H)-triamcinolone acetonide as tracer. The unagglutinated thymocytes (peanut negative) contained about 2 times more receptor sites per cell than agglutinated (peanut positive) ones (7650 +/- 1550 S.D. verus 3195 +/- 896 S.D.). The affinity for steroid was similar in both cell subsets, as was the stereospecificity for glucocorticoids, the time-course of steroid-receptor association, and cytoplasmic to nuclear translocation. Despite the greater number of glucocorticoid receptor sites, the peanut-negative thymocyte subpopulation did not differ from the peanut-positive one in its sensitivity to the inhibitory effects of triamcinolone acetonide, as determined by measurements of the incorporation of radiolabeled precursors of protein and DNA. Moreover, the peanut-negative subset appeared more resistant in vitro to the steroid-induced cell lysis as compared to the peanut-positive one. Thus, our data suggest that glucocorticoid receptor density and corticosensitivity are not directly correlated and that the number of glucocorticoid receptor sites may be dependent on the degree of immunologic maturation.

Binding Sites↗
PubMed1981

Imbalances in peripheral blood T-cell subpopulations in renal transplant patients.

The distribution of T-lymphocyte subpopulations bearing receptors for the Fc portion of IgG (TG) or IgM (TM) was monitored in 22 renal allograft recipients treated with immunosuppressive therapy and in 10 uraemic patients on haemodialysis. No significant difference in the distribution of T cells and T-cell subsets was found between normal controls and haemodialysed patients. In transplanted patients, however, a significant reduction of the total T-cell percentage (P less than 0.005), of TM subset percentage (P less than 0.025) and absolute number (P less than 0.005) and of TG absolute number (P less than 0.05) was observed. Considering patients with allografts functioning for more than 1 year only, the reduction in TM cells in terms of percentage (P less than 0.0005) and absolute number (P less than 0.025) was significant, while TG subset levels did not change significantly. In patients transplanted less than 1 year previous to our study, total T cells and T-cell subsets were reduced significantly only as absolute numbers. During the 1st year we observed several increments of TM values towards normal levels, especially in the first 2 months after transplantation. During this period, TM subset levels sharply increased at acute rejection crisis and returned to previous values with rejection reversal. Our results suggest that the TM subset plays a prominent role in the mechanisms involved in the immunological response to allografts, and therefore repeated TM cell monitoring could be useful in the follow-up of renal transplant patients.

Graft Rejection↗