PubMed Health⌕ Search

Biomedical subjects

M Ferrarini

Publications and source records attributed to M Ferrarini.

At least 127 records · Page 7Linked to original sources
PubMed1986

Presence of activated T-cells with a T8+ M1+ Leu 7+ surface phenotype in invaded lymph nodes from patients with solid tumors.

The lymphocyte surface phenotype of lymph nodes from patients with larynx or urinary bladder carcinoma was investigated by using a panel of monoclonal antibodies. The phenotype pattern of lymphocytes from lymph nodes invaded by malignant cells (as assessed by histopathology) was different from that of the cells from noninvaded or normal control nodes. Although the proportion of natural killer cells or macrophages was similar in the 3 groups of lymph nodes, invaded lymph nodes contained a higher proportion of T-cells and a lower B-cell percentage. Furthermore, cells from invaded nodes comprised 15-20% of T3+ T8+ cells that coexpressed the M1 marker and, to some extent, also the Leu 7 marker. A large proportion of cells with multiple markers were activated, as shown by the expression of Tac and HLA-DR antigens. In 2 patients activated T8+ cells expressing also M1 and Leu 7 markers infiltrated the tumor site. The presence of these activated cells both in involved nodes and tumor mass may indicate that they originate in response to cancer.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Large granular lymphocytes from patients with expanded LGL populations acquire cytotoxic functions and release lymphokines upon in vitro activation.

The phenotypic and functional features of purified large granular lymphocytes (LGL) from ten patients with LGL population expansions and cytopenias are described. The predominant LGL phenotypes were T3+, T8+, Leu-11+/-; however, in two patients, LGL expressed a T3-, Leu-11+ phenotype. Variable combinations of other LGL markers (OKM1, Leu-7), and HLA-DR were detected in individual cases. In nine of ten cases, freshly isolated LGL did not exert cytolytic activity for K562 target cells, but purified LGL cultured in the presence of recombinant interleukin 2 (rIL2) acquired potent cytotoxic activity in all cases tested. LGL did not proliferate in response to phytohemagglutinin (PHA). However, LGL released variable amounts of IL2 and gamma-interferon (gamma-IFN) after PHA stimulation. In some cases, stimulation of fresh LGL with recombinant IL2 induced production of gamma-IFN. No correlation was found between the functional capabilities and the original phenotype of the expanded LGL populations.

Antibodies, Monoclonal↗
PubMed1985

Maturation of chronic lymphocytic leukemia B cells: correlation between the capacity of responding to T-cell factors in vitro and the stage of maturation reached in vivo.

Circulating malignant cells from 15 patients with B-cell chronic lymphocytic leukemia (B-CLL) were examined by the electron microscope (EM) and tested for their capacity to produce immunoglobulin (Ig) molecules using endogenous labeling techniques in vitro. In agreement with previous observations, B-CLL clones from various patients could be subdivided in three distinct groups: immature (type 1) clones, that comprised mainly small resting lymphocytes which synthesized, but degraded Ig of the secretory type intracellularly; mature (type 3) clones consisting mainly of cells with an extended Golgi apparatus and numerous strands of rough endoplasmic reticulum (RER) that secreted Ig molecules; and clones (type 2) at an intermediate maturational stage. When stimulated with T-cell supernatants that contained T-cell replacing factor(s) (TRF), type 3 and, to a lesser extent, type 2 clones differentiated further and secreted increased amounts of Ig. This maturation was not observed when type 1 clones were stimulated with the same supernatants. However, these cells were not incapable of further maturation since they could differentiate in response to phorbol ester (TPA). The present data reinforce the concept that different CLL clones undergo a process of maturation in vivo that may be arrested at different levels and demonstrate that the various clones respond differently to physiological stimuli depending upon the level of maturation already reached in vivo.

B-Lymphocytes↗
PubMed1985

Kaposi's sarcoma and HTLV-III infection. Virus-like particles in skin lesions: experimental observations.

Skin biopsies from a subject affected by KS and AIDS were examined by means of EM. Samples were obtained both in correspondence of a typical nodule, and from an apparently normal area. The disease process had started at least 8 mo. before, and the patient showed a reduced number of OKT4 cells, with an inversion of the normal T4/T8 ratio. Besides that, high titre antibodies versus HTLV-III were present, whereas antibodies versus CMV and EBV were not demonstrable. Light and electron microscopy demonstrated the typical picture of KS, with marked proliferation of undifferentiated endothelial and spindle-like cells within a network of collagen fibers. Neoformed capillaries very rarely showed an organization comparable to small vessel of normal dermis. Retro-virus-like particles recalling the ones described in lymph-nodes of subjects affected by AIDS by Armstrong et al. (1984) were observed in the skin tissue obtained in correspondence of the Kaposi lesion; the same were either isolated or gathered in small groups within cytoplasmic vescicles. Similar particles were not evidenced in the tissue obtained from normal skin. The interpretation of morphological aspects requests of course a great caution. However the observation seems to be noteworthy, specially if one considers the demonstrated association between retro-virus of HTLV-III group and AIDS, and that its unusual frequency as well as the malignancy in an immunodepressed host are as yet poorly understood.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Large granular lymphocytes have a promoting activity on human peripheral blood erythroid burst-forming units.

Peripheral blood mononuclear cells were fractionated according to the expression of a variety of surface markers, and the fractions obtained were tested for erythroid burst-forming unit (BFU-E) colony formation. BFU-Es were detected in the HLA-DR+ non-T cell fraction, but gave rise to optimum colony numbers only in the presence of a nonadherent, relatively radioresistant cell. This accessory cell was found among the HLA-DR- non-T, non-B cells, a fraction that was particularly enriched in large granular lymphocytes (LGLs). Experiments carried out to assess directly the surface markers of the accessory cell revealed an FcR+, OKM1+, Leu 7+, Leu 11+, OKT4-, OKT8- surface phenotype, which is consistent with that of the majority of LGLs. Peripheral blood LGLs, purified by Percoll density gradient, proved very efficient in promoting optimal BFU-E colony formation. All of these results indicate that LGLs have a potent erythroid burst-promoting activity. Such activity is probably mediated through the release of soluble factors, as shown by the observation that LGL culture supernatants were as effective as LGLs in sustaining colony formation.

Antigens, Surface↗
PubMed1985

Production of B cell growth factor by a Leu-7+, OKM1+ non-T cell with the features of large granular lymphocytes (LGL).

The present study reports the characterization of a non-T cell from human peripheral blood which is capable of releasing BCGF. This BCGF-producing non-T cell had a T3-, T8-, Leu-7+, OKM1+, HLA-DR-, Leu-11- surface phenotype and was likely to belong to the so-called large granular lymphocyte (LGL) subset because: after fractionation of non-T cells according to the expression of Leu-7 or HLA-DR markers, it was found in the Leu-7+, HLA-DR- fractions that were particularly enriched in LGL; it co-purified with LGL on Percoll density gradients; and it expressed Leu-7 and OKM1 markers that are shared by a large fraction of LGL. Although co-purified with cells with potent NK capacities, the BCGF-producing cell was not cytotoxic, because treatment of Leu-7+ cells with Leu-11 monoclonal antibody and complement abolished the NK activity but left the BCGF activity unaltered. The factor released by this LGL subset was not IL 1 or IL 2 mistakenly interpreted as BCGF, because: a) cell supernatants particularly rich in BCGF activity contained very little or no IL 1 or IL 2; b) BCGF-induced B cell proliferation was not inhibitable by anti-Tac antibodies (this in spite of the expression of IL 2 receptor by a proportion of activated B cells); and c) BCGF activity was absorbed by B but not T blasts.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1984

Granule formation in large granular lymphocytes (LGL). Ultrastructural and cytochemical studies on cells from patients with abnormally expanded lgl populations.

The peripheral blood mononuclear cells from five patients with abnormally expanded populations of large granular lymphocytes (LGL) of possible malignant origin have been studied by electron microscopy. These cells had fewer granules than normal circulating LGL but displayed a variety of organelles possibly involved in the process of granule formation. This process apparently originated from the fusion of vesicles that had a characteristic cup-shape (and appeared to be derived from the Golgi apparatus) with smaller vesicles, mostly of the coated type. This fusion resulted in the formation of multivesicular bodies (MVB) whose limiting membrane was constituted by that of the cup-shaped vesicle. MVB gradually matured into electron-dense granules. A number of cup-shaped vesicles were found positive for the cytochemical localization of thiamine pyrophosphatase (TPP) activity that is a specific marker of the trans aspect of the Golgi apparatus, a finding which confirmed that they were Golgi-derived. The smaller, mostly coated, vesicles were positive for acid phosphatase (AP) and evidence was obtained indicating that they subserved the function of transporting acid hydrolases from the rough endoplasmic reticulum to the cup-shaped vesicles or to the MVB. The plasma membrane did not appear to contribute to MVB or granule formation since endocytic vacuoles induced by reacting the cell surface with the appropriate monoclonal antibodies (followed by peroxidase labelled anti-immunoglobulin) were never seen while fusing with granules or MVB. Rather, these vesicles formed secondary lysosomes after having encountered smooth or, more rarely, coated vesicles. Granulogenesis in LGL, therefore, resembles the process of granule formation observed in secretory cells. The active process of granulogenesis detected in the patient cells and a number of other findings indicate that they were LGL at early stages of maturation. The surface phenotype consistently found in these cells (OKT3+, Leu 1+, OKT8+, Leu 2a+, OKT11+, Leu 5+ and OKM1) is different from that of the majority of the normal LGL and may correspond to that of immature LGL.

Acid Phosphatase↗
PubMed1983

Expression of a receptor for sheep erythrocytes by B lymphocytes from a chronic lymphocytic leukemia patient.

A patient with a B-cell chronic lymphocytic leukemia, whose lymphocytes also formed rosettes with sheep red cells, is described. The B-cell nature of the malignant lymphocytes was determined by surface marker analysis, and cytochemical and ultrastructural studies. The lymphocyte membrane immunoglobulin (IgG1K) did not have anti-sheep red cell activity and was not responsible for the binding of sheep erythrocytes to the leukemic cells as shown by (i) the failure to inhibit rosette formation with anti-immunoglobulin reagents and (ii) the different sensitivity to proteolysis of the membrane immunoglobulin and the sheep erythrocyte receptor. The malignant lymphocytes expressed a receptor for sheep erythrocytes similar to that of normal T cells since they stained with monoclonal antibodies directed against the sheep red cell receptors. Furthermore these antibodies blocked rosette formation. Endogenous labeling experiments demonstrated that the patient's cells produced IgG both of the membrane and of the secretory type. The latter molecular form was also actively secreted. Ultrastructural studies demonstrated that the malignant clone comprised cells at different maturational stages and with different secretory properties. These findings were confirmed by the analysis of intracytoplasmic acid hydrolases, which are normally expressed at late maturational stages. These data are consistent with the hypothesis that a process of maturation was occurring within the malignant clone.

Aged↗
PubMed1983

Complement receptor distinguishes between two subsets of large granular lymphocytes with different natural killer activity and cytochemical and ultrastructural features.

Human peripheral blood large granular lymphocytes (LGL)--that is, cells with intracytoplasmic azurophilic (electron-dense) granules, with a positivity for the cytochemical localization of certain acid hydrolases, and with avid surface receptors for the Fc portion of IgG--have been purified on Percoll density gradients. Approximately 30% of these cells expressed receptors for the third complement component (C3R). They were separated into C3R-positive and C3R-negative cells. C3R+ cells had a significantly greater natural killer (NK) activity against K562 target cells than C3R+ cells. This difference was unrelated to the presence in the C3R+ cells of a contaminant cell type incapable of NK activity, since cytochemical and ultrastructural analysis revealed that C3R+ and C3R- fractions contained comparable LGL numbers. Agarose cytotoxicity assays at the single-cell level demonstrated that C3R+ LGL contained a large number of cells that bound to but did not lyse the target. The remaining fully cytotoxic C3R+ LGL had, however, the same killing and recycling properties as the cells from the C3R fraction. Electron microscopy and cytochemical studies showed that C3R+ cells had fewer electron-dense granules than C3R cells and stained more faintly for the localization of alpha-naphtyl acetate esterase. In contrast to C3R cells, C3R+ LGL displayed morphological features suggesting that an active process of granule formation was taking place. Taken together, the data indicate that C3R+ cells represent a discrete subset or a maturational stage of LGL.

Antibodies, Monoclonal↗
PubMed1983

In vitro selective expansion of allergen specific T cells from atopic patients.

Peripheral blood mononuclear cells from atopic donors were stimulated in vitro with allergens (Rye group I or Dermatophagoides pteronyssinus). T cell lines were originated and maintained in long term culture using IL-2 and periodical restimulations with allergen. The lines were antigen specific (i.e. responded to the allergen used to raise them and not to other antigens) and required that the antigen was presented by autologous cells (i.e. they were restricted). The restriction elements were probably at the level of HLA-DR antigens since the proliferative response was specifically blocked by anti-HLA-DR antibodies. Surface marker analysis revealed that the lines comprised mainly cells with an helper/inducer phenotype, although cells with markers of the suppressor/cytotoxic T cells were also present. The lines could be cloned by limiting dilution and clones with the same restriction and specificity as the parental line were isolated. These studies demonstrate the possibility of obtaining a large number of allergen specific human T cells that can be used for further in vitro studies on the regulation of the IgE response.

Allergens↗
PubMed1983

Augmentation of human peripheral blood natural killer activity by methisoprinol.

Methisoprinol (MIP) was found to augment natural killer (NK) activity of peripheral blood mononuclear cells (PBMC), as measured in a 4-h 51Cr release assay using K562 cells as targets. Overnight incubation of PBMC with 0.1 microgram/ml MIP, followed by removal of the drug, resulted in significant increases in the NK activity of all 17 donors studied. Augmentation of NK, expressed as lytic units (LU)/10(7) effector cells, was generally two- to fourfold, and was manifest as early as 1 h after incubation with the drug, but was maximal after 4 h. The effect of MIP was dose dependent up to 0.1 microgram/ml and remained at a plateau up to 10 micrograms/ml, where cytotoxicity to the effectors was observed. The effect of MIP was exerted on the effector cells and was not due to an increased susceptibility of target cells to lysis. In addition, this phenomenon was probably independent of interferon (IFN) production. Binding and killing at the single-cell level were shown to be unaffected by prior treatment with MIP. Rather, the analysis of the kinetics of NK activity indicated that MIP increased the recycling ability of NK effector cells. Augmentation of NK by MIP was dependent on the presence of adherent cells in PBMC fractions. Populations depleted of plastic adherent cells or populations enriched for adherent cells themselves could not undergo boosting by MIP, indicating that MIP did not act to recruit functional cells from inactive precursors. These studies suggest that the observed antiviral and/or immunoregulatory actions of MIP might be mediated through an increased NK cell activity.

Cell Adhesion↗
PubMed1983

PHA-induced human T cell colony formation: enhancing effect of large granular lymphocytes.

The capacity of phytohemagglutinin (PHA)-stimulated human T cells to develop into colonies in agar has been evaluated in the presence or absence of a variety of peripheral blood mononuclear cell subsets. A subpopulation of non-T, non-B cells with receptors for the Fc portion of IgG (i.e. third population cells or TPC) was found to enhance considerably the T cell colony forming capacity. Since TPC have been previously shown to be highly enriched for large granular lymphocytes (LGL, i.e. cells with cytoplasmic azurophilic granules and acid hydrolases), LGL were purified on Percoll density gradients and tested for their T cell colony enhancing capacity. It was shown that LGL were indeed the cells capable of enhancing the T cell colony formation.

Cell Separation↗
PubMed1983

Differentiation of chronic lymphocytic leukemia cells: correlation between the synthesis and secretion of immunoglobulins and the ultrastructure of the malignant cells.

The capacity of synthesizing and secreting Ig molecules was studied in 11 patients with B-cell chronic lymphocytic leukemia (B-CLL) whose cells expressed surface IgM, in 3 patients with surface IgG-bearing cells, and in 2 IgM prolymphocytic leukemias (IgM-PLL). Three types of mu chains were detected by SDS-polyacrylamide gel electrophoresis analysis of the endogenously labeled molecules isolated by specific immunoprecipitation. Two of them were isolated from the cell lysates and were identified as the membrane mu chain and the precursor of the secreted molecules, respectively. The latter also possibly contained precursors of the membrane molecules. The third type of molecule was detected only in the culture medium and was identified as secretory mu chain. Not all of the malignant clones possessed the three types of mu chains. Only 7/13 of the IgM-bearing malignant cell clones were capable of secretion, whereas the remaining synthesized the secretory mu chains but degraded them intracellularly. Two types of molecules (membrane and secreted) were found in the IgG-bearing CLL cells from three patients. In all of them, secretion was detected. Ultrastructural analysis demonstrated that cells from the secreting clones had the features of more mature lymphocytes than the cells from nonsecreting clones. These features were represented by a developed Golgi apparatus, various types of vesicles (smooth and coated), and strands of the rough endoplasmic reticulum. A certain heterogeneity of the degree of maturation of the cells was observed within these clones. The data are consistent with the hypothesis that CLL clones are heterogeneous and can be distinguished through the different degrees of maturation of their cell components.

Antibodies, Anti-Idiotypic↗