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Biomedical subjects

R Zambello

Publications and source records attributed to R Zambello.

126 records · Page 7Linked to original sources
PubMed1987

Immunologic abnormalities in angioimmunoblastic lymphadenopathy.

In this study we describe the results of phenotypic, serologic, and functional analyses performed in nine patients with angioimmunoblastic lymphadenopathy (AILD). The study investigates the nature of the T-cell defects which seem to represent a consistent feature in this disease. The study, based on the analysis of T-cell subsets with monoclonal antibodies and on functional in vitro tests, showed the following main abnormalities: reduction of the absolute number of circulating T-cells; inversion of the CD4/CD8 ratio, both in the peripheral blood and in the involved lymph nodes; high percentages of activated T-cells (CD8+/HLA-DR+); defective T-cell response in vitro to the PHA mitogen; and minimal helper and enhanced in vitro suppressor functions. Some of these immunologic dysfunctions are also observed in acquired immune deficiency syndrome (AIDS) which has in common with AILD several clinical features. However, no evidence of HTLV-III infection could be demonstrated in our patients with AILD.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Pulmonary alveolar macrophages in patients with sarcoidosis and hypersensitivity pneumonitis: characterization by monoclonal antibodies.

Using a panel of monoclonal antibodies (MoAbs), the frequency of cells bearing Class I and Class II major histocompatibility complex (MHC) determinants, transferrin receptor (TR) sites, and interleukin-2 receptors (IL-2R) has been evaluated on pulmonary alveolar macrophages (PAM) recovered from the bronchoalveolar lavage (BAL) fluid of 21 patients with pulmonary sarcoidosis (including 11 cases with active sarcoidosis and 10 cases with inactive disease), 8 patients with hypersensitivity pneumonitis (HP), and 6 normal non-smoking volunteers. When the frequency of Class II DR-positive cells was considered, 64.3% of control PAM expressed HLA-DR products. No statistically significant differences were observed between controls and sarcoid patients, while HP patients showed an enhanced proportion of DR+ PAM with respect to normal PAM (P less than 0.05). On the contrary, the frequency of PAM expressing HLA-DQ molecules was higher in both active sarcoidosis and HP patients with respect to patients with inactive sarcoidosis and normal subjects (P less than 0.001). A statistically significant increase in Class I antigen-positive PAM has been demonstrated in HP patients as compared to controls (P less than 0.05). Active sarcoid patients showed a higher number of PAM-bearing TR sites than controls and other groups of patients considered (P less than 0.001). An increase in the percentage of IL-2R-positive PAM has been demonstrated in active sarcoidosis (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1987

Alpha-interferon activated cytotoxic lymphocytes in hairy cell leukemia patients: evaluation of cytotoxic events.

To further define the mechanisms responsible for the alpha-interferon (alpha-IFN) efficacy in the treatment of hairy cell leukemia (HCL), experiments were carried out to specify the cytotoxic events taking place following this type of therapy. Although an increased natural killer (NK) activity was demonstrable after alpha-IFN treatment, evidence has been provided that hairy cells were not specifically lysed either by fresh autologous/allogenic NK lymphocytes or by lymphokine activated killer (LAK) cells. This property could not be induced in vitro by alpha-IFN or by interleukin-2 (IL-2). Our data favour the hypothesis that the increase of NK cell activity observed following alpha-IFN therapy has not a direct antineoplastic effect but is likely to be of relevance for a non-specific enhancement of the host immune system. In alpha-IFN treated HCL this latter property may account for the better resistance to infections which usually represents the major cause of mortality in these patients.

Adult↗
PubMed1987

Rearrangement for the T-cell receptor gene and co-expression of immature T-cell markers and natural killer cell phenotype, in a patient with acute lymphoblastic leukaemia.

We describe a patient with acute lymphoblastic leukaemia whose blasts co-expressed immature T-cell markers and nearly the entire phenotypic repertoire of NK cells. The T-cell nature of the proliferating blasts was proven by the demonstration of the rearrangement for the beta-chain of the T-cell antigen receptor. Although an abnormal phenotypic expression related to the neoplastic proliferation cannot be formally excluded, it is possible that the cells in this patient may represent the clonal expansion of a normal subpopulation of T-cell lineage NK-related cells frozen at an early stage of differentiation. These features provide arguments for discussing the controversial issue of the ontogeny of NK cells and their relationship to the T-cell lineage.

Acute Disease↗
PubMed1987

High serum levels of soluble interleukin-2 receptors in sarcoidosis.

We provide evidence that high levels of soluble interleukin-2 receptor (sIL-2R) are present in the serum of patients with sarcoidosis. Because sIL-2R is capable of binding to its ligand (IL-2), the increased serum levels of this molecule could induce a starvation of IL-2. This mechanism could help to explain a number of immunological abnormalities extensively reported in these patients and generally attributed to not yet identified serum inhibitory factors.

Adult↗
PubMed1987

High serum levels of soluble interleukin 2 receptor in patients with B chronic lymphocytic leukemia.

By using an enzyme-linked immunosorbent assay, the presence of the soluble form of the interleukin-2 receptor (sIL-2R) was evaluated in the peripheral blood of 54 patients with B cell chronic lymphocytic leukemia (B-CLL). Serum levels of sIL-2R were correlated with clinical features, relevant hematologic and immunological data, and in some cases, with in vitro functional studies. In 51 patients (94.4%), the levels of sIL-2R were increased as compared with normal age-matched controls (1,781 U/mL +/- 231 v 276 U/mL +/- 26, respectively; P less than .001). Although this increase was observed in all stages of the disease and independently of several hematologic and immunologic parameters, a trend toward lower levels of sIL-2R was documented in patients with a less-invasive disease. When the values were correlated with the functional status of the residual T cell population, it was found that patients with the lowest levels of sIL-2R showed the best mitogenic response and helper capacity. It is suggested that in B-CLL patients the high levels of serum sIL-2R, capable of binding to its ligand, may block the T cell-produced IL-2, thus contributing toward a defective physiological action by this lymphokine. In turn, this defective availability of IL-2 may play a part in the abnormal immunoregulation that is implicated in the hypogammaglobulinemia, susceptibility to infections, and incidence of second neoplasias often observed in this disease.

Aged↗
PubMed1987

Cytotoxic in vitro function in the lymphoproliferative disease of granular lymphocytes.

In 20 patients with lymphoproliferative disease of granular lymphocytes (LDGL) the cytotoxic in vitro function of peripheral blood mononuclear cells was studied against both NK sensitive (K-562) and NK resistant target cells (Daudi). Cytotoxicity was analysed at resting conditions and after in vitro pre-incubation with recombinant alpha 2-interferon, gamma-interferon and interleukin 2. At resting conditions, a heterogeneous cytotoxic picture was observed against the K-562 targets, with 11 of the 20 patients showing a normal or increased NK activity, and nine an impaired function. Against the Daudi targets, unstimulated cells from all patients displayed a normal cytotoxic activity. Following in vitro stimulation, an increased lytic function against K-562 cells was demonstrated in six of the nine patients with low basal values, in three after boosting with all lymphokines tested and in three with interleukin 2. In three of these six patients incubation with interleukin 2 also produced an increased cytotoxic function against Daudi target cells; this phenomenon may be associated to the lymphokine-activated killer (LAK) system. The importance of investigating the cytotoxic in vitro function in LDGL patients to further characterize the biological features of GL and its relevance to better define the nature of this disease are discussed.

Adult↗
PubMed1986

Lung T cells in hypersensitivity pneumonitis: phenotypic and functional analyses.

Cells recovered from bronchoalveolar lavage (BAL) and tissue sections from transbronchial lung biopsies were studied in 16 patients with symptomatic hypersensitivity pneumonitis (HP) and in six subjects with a similar history of exposure but without features of disease by using a series of monoclonal antibodies (MoAb) detecting different lymphocyte subpopulations, including T and T subsets, B lymphocytes, and natural killer (NK) cells. Their functional activities in cytotoxic and suppressor assays and the microenvironment in the lung by using immunohistological techniques were also evaluated. It has been demonstrated that the majority of cells recovered from BAL of HP patients are represented by T8 lymphocytes, with a relevant imbalance of the T4/T8 ratio (p less than 0.001). HNK-1+ cells were markedly increased (p less than 0.001), whereas the frequency of cells bearing other NK-related markers (NK-15, VEP 13, Ab8.28, T10, M1, and Fc gamma R) were not significantly increased with respect to controls. Immunohistological study confirmed that the majority of cells infiltrating lung parenchyma are T8+ lymphocytes. The number of HNK-1+ cells detected on lung biopsies was very low in all cases, even in patients with the highest values on BAL suspensions. The evidence of cells bearing the proliferation-associated markers (Tac and T9 antigens) seems to support the hypothesis of a local proliferation in the lung. In terms of phenotypic analysis, the results observed in the group of asymptomatic individuals are qualitatively superimposable on those observed in the HP group, but the magnitude of the phenomenon is less prominent and therefore the data are not as statistically significant as that produced by the comparison between HP patients and the same controls. Functional analysis of BAL T cells from both HP patients and asymptomatic individuals showed suppressor activity in vitro, as determined by the ability to influence a pokeweed mitogen (PWM)-driven B cell differentiation assay. BAL cells from HP patients were also able to display a definite cytotoxic function in vitro, whereas BAL lymphocytes from asymptomatic subjects did not. Taken together, these data demonstrated that cells responsible for the alveolitis in patients with HP are characterized by the expansion of T cells with the phenotype and functions of both suppressor and/or cytotoxic lymphocytes. This expansion is likely to be related to a local immunologic response to the antigenic stimulus and may provide new insights into the pathogenetic mechanisms of this disease, its pathological pattern, and its management.

Adult↗
PubMed1986

Activated T cells with immunoregulatory functions at different sites of involvement in sarcoidosis. Phenotypic and functional evaluations.

Cells from recovered BAL fluid and from infiltrates in different involved tissues (lungs, lymph nodes, conjunctiva, liver, spleen, and skin) were studied in 22 patients with active sarcoidosis in order to define the surface phenotype, functional in vitro properties, and topographic distribution of the cells in granulomatous lesions. Our data demonstrated a compartmentalization of activated T cells with immunoregulatory functions from the blood to all sites of disease activity. In fact, these cells were found to express the T4+ Leu 8- 5/9+ T17- phenotype, which belongs to cells with helper activity, and that provide heightened responses in functional assays of helper activity, IL-2 release, and the ability to respond in AMLR's. Both a cellular redistribution and a local in vitro replication account for this tissue compartmentalization in sarcoidosis. The microanatomic location of activated T cells, as defined by immunohistological evaluation, showed that the state of activation in these T cells may be a consequence of an intimate contact between helper cells and macrophages within the sarcoidosis granulomas.

Adult↗
PubMed1986

Peripheral blood NK cells in patients with extrinsic allergic alveolitis: phenotype and function.

Peripheral blood mononuclear cells obtained from patients with extrinsic allergic alveolitis were tested with a series of monoclonal antibodies against natural killer cells, including HNK-1, NK-15, Ab8.28, OKM1 reagents. An NK in vitro functional evaluation of these cells was associated to the phenotypic analysis. Our data demonstrated an increase, with respect to controls, of the percentage and absolute number of HNK-1 positive cells in the blood of these patients. This increase was consistent with an enhanced cytotoxic in vitro activity. These findings provide evidence that in patients with extrinsic allergic alveolitis, the exposition to antigenic stimuli triggers the NK system. Possible immunopathogenetic mechanisms, especially in comparison with other interstitial lung disorders, are discussed.

Adolescent↗
PubMed1986

The acquired immunodeficiency syndrome (AIDS): insights into the immunopathogenesis of the pulmonary involvement.

The lung is involved in more than 50 per cent of patients with the acquired immune deficiency syndrome (AIDS), and pulmonary abnormalities can be easily investigated using the bronchoalveolar lavage (BAL). Besides providing information on the type of infecting microorganism, BAL has been used to characterize immunocompetent cells from the lower respiratory tract in these patients. This allows new insights into the immunopathogenetic mechanism involved in the persistence of opportunistic pulmonary infections and in the uncontrolled viral replication. This paper emphasizes the value of BAL evaluation as a simple and useful method for investigating the involvement of the distal respiratory tract in AIDS patients. A particular attention is payed on the immunological pulmonary abnormalities of this epidemic immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Alpha-interferon activates the natural killer system in patients with hairy cell leukemia.

To elucidate the mechanisms of alpha-interferon's (alpha-INF) therapeutic effect on clinical and laboratory findings in hairy cell leukemia, we sequentially monitored different immunologic parameters in three patients treated with recombinant alpha-INF. The most evident effect of this treatment on the immune system was the recovery of natural killer (NK) cell in vitro activity of peripheral blood lymphocytes, which was severely impaired before therapy. In particular, NK function began to improve after 3 months, and a complete recovery was obtained after 6 months in all cases. This increase parallels the improvement in clinical and laboratory findings.

Adult↗
PubMed1986

The analysis of expanded cells from patients with lymphoproliferative disorders of granular lymphocytes may help to clarify the NK cell differentiation.

Surface phenotype and functional in vitro activities were studied in 2 cases of lymphoproliferative disorders of granular lymphocytes. Cells from both patients presented the same, previously unreported, surface phenotype (i.e. T3+, T8+, T4-, HNK-1-, NK-15+, M1-), were unable to display either Natural Killer (NK) activity or suppressor function in a poke-weed-driven system, and showed a defective response to phytohemagglutinin (PHA). On the basis of available schemes for NK cells ontogenesis, we will discuss the phenotype and functional activities of patients' cells suggesting that the cell population expressing the T3+, T8+, HNK-1-, NK-15+, M1- phenotype might represent a discrete stage along the NK-cell differentiation pathway.

Antigens, Surface↗
PubMed1985

Phenotypical and functional analysis of natural killer cells in sarcoidosis.

The frequency of cells reactive with natural killer (NK)-related monoclonal antibodies (MoAbs) HNK-1, NKP-15, B73.1, VEP-13, Ab8.28 has been evaluated in the peripheral blood and bronchoalveolar lavage (BAL) fluid of 39 patients with pulmonary sarcoidosis (including 19 cases with active sarcoidosis and 20 cases with inactive disease). This phenotypic analysis was carried out together with the NK in vitro functional evaluation of cell populations from peripheral blood and BAL fluid. In addition, inhibition studies were performed in order to evaluate the ability of alveolar macrophages (M phi) to modulate NK activity. Data from peripheral blood showed an increased number of mononuclear cells bearing HNK-1, NKP-15, Ab8.28, VEP-13, and B73.1 determinants in patients with active sarcoidosis with respect to patients with inactive disease and controls. The majority of HNK-1-positive cells lacked both Leu2 and Leu3 antigens when investigated in a double marker system. A parallel increase in the in vitro cytotoxicity assay has been demonstrated. On the other hand, only a few mononuclear cells recovered from BAL fluid displayed a surface pattern of NK cells. This small population of HNK-1-positive cells expresses the HNK-1/Leu3 phenotype and does not exhibit NK activity. The alveolar M phi from sarcoid patients, as well as alveolar M phi from controls, have the property of inhibiting the NK activity of autologous peripheral blood lymphocytes. The lack of lung NK function in patients with active sarcoidosis may be related to the presence of immature forms of NK cells and/or to the release of soluble factors by alveolar macrophages.

Adult↗
PubMed1985

Bronchoalveolar lavage and lung histology. Comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.

To determine whether bronchoalveolar lavage reflects the histologic aspects of the lung histology in patients with sarcoidosis and hypersensitivity pneumonitis, cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 33 patients. The evaluation of cellular types and their topographic distribution in situ was determined by using monoclonal antibodies in combination with immunohistochemical techniques. Cell counts in bronchoalveolar lavage and lung biopsies were significantly correlated both in sarcoidosis and hypersensitivity pneumonitis. In fact, the relative proportions of inflammatory and immunocompetent cells recovered from lavage fluid accurately overlapped those observed in lung tissue sections. However, in patients with more pronounced alveolitis, the frequency of macrophages in tissue sections was higher than that observed in the bronchoalveolar lavage, and the degree of lymphocytes in the lavage was higher than that observed in the corresponding biopsy. Specifically, in these patients the lavage underestimated the amount of macrophages in the lung biopsies and overestimated the number of lymphocytes that were present in the lung parenchyma. This was more evident in patients with hypersensitivity pneumonitis, where the intensity of alveolitis was higher than in sarcoidosis. Our data support the idea that, at least in patients with sarcoidosis and hypersensitivity pneumonitis, bronchoalveolar lavage correctly samples the alveolitis. Discrepancies in patients with very high intensity alveolitis could be due to a more pronounced recirculation of lymphocytes from the parenchyma to the alveolar spaces.

Adolescent↗
PubMed1985

Impaired production of interleukin-2 in peripheral blood of patients with sarcoidosis.

In twelve patients with active sarcoidosis we attempted to explain the nature of reduced release on interleukin-2 (IL-2) and the consequent impairment in lymphoproliferative in vitro responses. The addition of exogenous IL-2 containing supernatants was unable to completely restore the defective uptake of 3H-Thymidine suggesting that an impairment of IL-2 producer cells is not enough to explain the in vitro hyporesponsiveness of sarcoid lymphocytes. We also found a reduced number of precursors of IL-2 responder cells, as defined by peripheral blood lymphocytes bearing Tac determinant following in vitro stimulation with mitogens. The abnormalities of both IL-2 producer cells and precursors of IL-2 responder cells in peripheral blood of patients with sarcoidosis are discussed, stressing the importance of the concept of compartmentalization of T lymphocytes in this disease.

Adult↗
PubMed1984

Evidence of cells bearing interleukin-2 receptor at sites of disease activity in sarcoid patients.

The frequency of cells reactive with anti-Tac monoclonal antibody (MoAb), which recognizes the interleukin-2 (IL-2) receptor, has been evaluated in cell suspensions from peripheral blood and bronchoalveolar lavage (BAL), and in frozen sections from involved tissues in 18 patients with active sarcoidosis. Peripheral blood lymphocytes of sarcoid patients do not bear Tac determinant and reduced numbers of Tac+ cells are inducible following PHA stimulation. On the other hand, significant numbers of lymphocytes reactive with anti-TacMoAb are present in the cells obtained from the BAL and a number of Tac+ cells infiltrate the lung, lymph node and conjunctiva. The finding of Tac+ cells in the BAL fluid and in other organs in patients with sarcoidosis provides evidence that some T cells in these involved tissues have the characteristics of IL-2 responder cells and thus the potential to absorb IL-2, supporting the hypothesis that T lymphocytes replicate in situ at sites of disease activity.

Adult↗