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Biomedical subjects

A Risso

Publications and source records attributed to A Risso.

32 records · Page 2Linked to original sources
PubMed1986

Different expansions of T lymphocyte subpopulations in the lung and corticosteroid-induced changes in patients with active pulmonary sarcoidosis.

Pulmonary sarcoidosis is a disease characterized by increased numbers of T lymphocytes within the alveolar structures and the consequent spontaneous release of a variety of mediators relevant to the pathogenesis of this disorder. This phenomenon is associated with a different expansion of the T cell subpopulations present in the lung. Using monoclonal antibodies specific for T cell subsets with helper functions, we have evaluated the different T lymphocyte subpopulations present in patients with active and inactive pulmonary sarcoidosis. The small fraction of helper T cells recognized by the 5/9 monoclonal antibody appear to be preferentially expanded in the lung of patients with active disease. The functions of the 5/9+ lung T cells in pulmonary sarcoidosis were evaluated by considering the spontaneous release of monocyte chemotactic factor, the help in immunoglobulin production, and the spontaneous production of interleukin-2 by the 5/9+ lung T cells from patients with active disease. These T cell functions appeared to be restricted to the 5/9+ T cell subset. The sensitivity of the 5/9+ lung T cells to corticosteroid treatment in pulmonary sarcoidosis was studied by performing bronchoalveolar lavage in patients with active disease before and after oral prednisone therapy. Evaluation of lymphocyte subsets after 3 months of therapy showed a marked reduction of 5/9+ T cell percentages even though the overall proportion of lavage cells that were T lymphocytes was still elevated. Thus the 5/9 monoclonal antibody may be considered a good marker in gauging the activity of the alveolitis in pulmonary sarcoidosis because it recognizes the T cell subsets responsible for many activities relevant to the pathogenesis of this disorder. In addition, analysis of the proportions of 5/9+ lung T cells may result in a useful means to evaluate the early response to therapy.

Adrenal Cortex Hormones↗
PubMed1986

Helper T-lymphocytes in pulmonary sarcoidosis. Functional analysis of a lung T-cell subpopulation in patients with active disease.

Pulmonary sarcoidosis is a disease characterized by increased numbers of T-lymphocytes in the alveolar structures, which through the production of lymphokines modulate granuloma formation and polyclonally activate B cells to secrete immunoglobulins. The T-lymphocyte alveolitis is associated with a different expansion of various T-cell subpopulations identified by different monoclonal antibodies. Patients with active disease have increased numbers of helper T cells in the lungs, recognized by the OKT4 monoclonal antibody and decreased numbers of suppressor OKT8-positive lung T cells, whereas patients with inactive disease have increased numbers of OKT8-positive T cells and decreased numbers of OKT4-positive T cells in the lungs. Using the IgG fraction of a monoclonal antibody called 5/9, which reacts in normal subjects with approximately 30% of the OKT4-positive T-lymphocytes, it has been shown that the 5/9-positive T cells appear preferentially expanded in pulmonary sarcoidosis at sites of disease activity. To evaluate the functions of the T-cell subpopulation identified by the 5/9 monoclonal antibody in pulmonary sarcoidosis, we studied the unfractionated T-lymphocytes and the 5/9-positive and the 5/9-negative T-cell fractions in bronchoalveolar lavage of 12 patients with active lung disease. On T-cell suspensions, the spontaneous release of monocyte chemotactic factor and the polyclonal activation of autologous peripheral blood lymphocytes were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Functional characterization of a regulatory human T-cell subpopulation increasing during autologous MLR.

The present study was undertaken to investigate the heterogeneity of helper T cells in humans using two different monoclonal antibodies: 5/9 and MLR4. The former identifies 15-20% of resting T lymphocytes from peripheral blood and corresponds to an anti-helper/inducer T cell. The second antibody, MLR4, recognizes 5% of total T lymphocytes and partially overlaps with the 5/9+ T cells. In order to investigate functional differences within the 5/9+ cells, we separated two different subsets (5/9+ MLR+ and 5/9+ MLR4-) by a rosetting technique. Although both subsets provide help for Ig synthesis in a PWM-stimulated culture, only the 5/9+ MLR4- fraction gave a proliferative response in both autologous and allogeneic MLR and to soluble protein antigens. The effect of radiation on the ability of the two subsets to provide help for Ig synthesis showed that the 5/9+ MLR4+ subset is highly radiation-sensitive, while 5/9+ MLR- is relatively radiation-resistant. In a further series of experiments, 5/9+ MLR4+ cells isolated after activation in an autologous MLR but not by Con A, were no longer able to induce T-cell differentiation but now showed a strong suppressor effect. The 5/9+ MLR4- subset separated from the same cultures did not display any suppressor function. These data demonstrate in fresh PBL the existence of a radiation-sensitive regulatory subset exerting a helper activity, and which acquires suppressor activity after activation in autologous MLR.

Antibodies, Monoclonal↗
PubMed1985

T-derived colony-inhibiting activity: partial characterization and mechanism of action.

A soluble inhibitor of granulocyte macrophage colony growth, to which we shall refer to as T-derived colony-inhibiting activity (Td/CIA), was obtained from the supernatant of T cells from 5 healthy donors and 5 patients with severe aplastic anemia (SAA) in remission, following immunosuppressive therapy. The supernatants were purified by an ACA 44 column and the suppressor activity found in fractions of 70,000-80,000 daltons. Experiments were then performed to test for endogenous productions of Td/CIA in normal marrow cells (NBM), reversibility of suppression, and competitive inhibition with human placenta-conditioned medium (HPCM). The results of this study can be summarized as follows: the endogenous production of Td/CIA can be elicited by addition of mitogens to NBM, and is prevented if the marrow is T-depleted or treated with cyclosporin A; suppression is completely reversible if Td/CIA is removed from NBM by washing at 1, 48, 72 and 96 h; CFU-c which have been exposed to Td/CIA once, and freed from Td/CIA by washing, are still sensitive to a second exposure of Td/CIA; there is no clear competitive inhibition between Td/CIA and HPCM. These experiments represent an in vitro model of a lymphokine-mediated regulation of CFU-c growth not associated with death of progenitor cells.

Bone Marrow Cells↗
PubMed1984

Autoimmune thyroid disease: purification and phenotypic analysis of intrathyroid T cells.

A phenotypic analysis of T cells infiltrating the thyroid of patients with autoimmune thyroid disease (both Graves' disease and Hashimoto's thyroiditis) was performed. T lymphocytes were purified from mononuclear cells extracted from surgically removed tissue. The following markers were evaluated: la antigens, MLR4 antigen (expressed on activated T cells) 5/9 antigen (expressed on a subset of lymphocytes containing the whole "helper-inducer" activity in vitro), Fc gamma-receptors, B9 antigen (expressed by cytotoxic, or precursor of cytotoxic, T cells). We observed increased percentages of 5/9-, MLR4- and la-positive T cells with respect to peripheral blood in both HT and GD: on the contrary, in specimens from nonautoimmune thyroid diseases mononuclear infiltrate was minimal, and even T cell evaluation was not possible. In addition, B9- and Fc gamma-positive T cells were increased in Hashimoto's, but not in Graves' thyroid tissue, thus suggesting a different role of cytotoxic effector mechanisms in the two diseases.

Adult↗
PubMed1976

Membrane Ig on MPC11 myeloma cells: correlation between the expression of membrane Ig, a receptor for Ig and the process of secretion.

The expression of membrane immunoglobulin (mIg) was examined in three cloned MPC11-derived mouse myeloma cell lines. Membrane immunofluorescence studies demonstrated that IgG2b producer cells (P1) had complete IgG molecules, L-chain producer (L1) had only L-chain determinants and nonproducer (NP2) did not have any Ig determinants on the cell surface. An Ig receptor, with characteristics different from B lymphocyte Fc receptor, has been found to be present on secreting cells (P1 or L1), but not on the NP2 cell variant. The data reported in the present paper indicate that the expression of mIg and of the Ig receptor molecule is clearly correlated with the process of secretion. In the light of previous data reported on Ig secretion, a model is proposed which correlates the process of secretion with the expression not only of mIg, but also of the receptor for Ig.

Binding Sites, Antibody↗
PubMed1976

A study of immunoglobulin classes present on the membrane and in the cytoplasm of human tonsil plasma cells.

The problem of whether immunoglobulin (Ig)-containing plasma cells expressed membrane Ig has been investigated using cells from human tonsils. In tonsils, IgG-containing cells are predominant, but a certain number of IgM, IgA and IgD-containing cells are also present. By using a double staining immunofluorescent technique for the simultaneous detection of membrane and intracytoplasmic Ig, it has been possible to ascertain that the large majority of IgA, IgM and IgD-containing cells had membrane immunoglobulin (mIg) of a class coincident with that of intracytoplasmic Ig. In addition a noticeable proportion of IgM-containing cells expressed membrane IgD, thus indicating that a certain number of these cells bore both membrane IgM and IgD. About 60% of IgG-containing cells had membrane IgG, while the remaining cells did not express mIg. Furthermore the surface staining of these cells was generally fainter than that of the cells containing other Ig classes. Experiments on the surface light chain type expressed by the single Ig-containing cells (IgCC) as compared to that found in the cytoplasm have shown that in the large majority of IgCC the light chain type of mIg coincided with that of intracytoplasmic Ig. Discordant light chain types of membrane and cytoplasmic Ig were found on about 12% of IgCC only. These values can be taken as a measure of how many IgCC had passively acquired mIg.

Cytoplasm↗
PubMed1975

Lymphocyte membrane receptors in human lymphoid leukemias.

Membrane-bound immunoglobulins, receptors for the Fc fragment of IgG and receptors for the third component of human or murine complement were used as B cell membrane markers to study peripheral blood lymphocytes from twenty-two patients with chronic lymphatic leukemia (CLL), five patients with acute lymphoblastic leukemia (ALL) and one patient with Sézary syndrome. The capacity of human T cells of forming "spontaneous rosettes" with sheep erythrocytes was employed as T cell membrane marker. In nineteen out of twenty-seven CLL or ALL cases tested a larger percentage of cells than that found in normal individuals expressed at least one of the three B cell membrane markers studied. In the patient with Sézary syndrome the percentage of cells forming "spontaneous rosettes" with sheep erythrocytes was larger than the normal, while cells bearing B cells markers were below the normal values.

Binding Sites↗
PubMedDate not supplied

A novel protocol that allows short-term stem cell expansion of both committed and pluripotent hematopoietic progenitor cells suitable for clinical use.

To obtain long-term engraftment and hematopoiesis in myeloablated patients, the cell population used for hematopoietic reconstitution should include a sufficient number of early pluripotent hematopoietic stem cells (HSCs), along with committed cells from the various lineages. For this purpose, the small subset of CD34+ cells purified from different sources must be expanded ex vivo. Since cytokines may induce both proliferation and differentiation, expansion would provide a cell population comprising committed as well as uncommitted cells. Optimization of HSC expansion methods could be obtained by a combination of cytokines able to sustain renewal of pluripotent cells yet endowed with poor differentiation potential. We used variations of the combinations of cytokines described by Brugger et al. [W. Brugger, S. Heimfels, R. J. Berenson, R. Mertelsmann, and L. Kanz (1995) N. Engl. J. Med. 333, 283-287] and Piacibello et al. [W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta (1997) Blood 89, 2644-2653] to expand UCB CD34+ cells and monitored proliferation rate and phenotype after 14 days of culture. Several hematopoietic lineage-associated surface antigens were evaluated. Our data show that flt3L and thrombopoietin in combination with IL-3, while sustaining a high CD34+ proliferation rate, provide a relatively low enrichment in very early uncommitted CD34+/CD38- cells. Conversely, in the absence of IL-3, they are less effective in inducing proliferation yet significantly increase the number of CD34+/CD38- cells. A combination of the above protocols, applied simultaneously to aliquots of the same sample, would allow expansion of both committed and pluripotent HSC. This strategy may represent a significant improvement for clinical applications.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

The interstitial lung disease associated with rheumatoid arthritis: evidence for imbalance of helper T-lymphocyte subpopulations at sites of disease activity.

Rheumatoid arthritis (RA) is a generalized disorder characterized by chronic inflammation of peripheral joints and by involvement of many organs, including the lung parenchyma. The inflammatory infiltrates of the rheumatoid synovial membranes are associated with increased numbers of T-lymphocytes, with increased proportions of helper (OKT4 positive) T-cells and decreased percentages of suppressor/cytotoxic (OKT8 positive) T-cells, and since patients with interstitial lung disease associated with RA often have increased numbers of lymphocytes in the alveolar structures, it seemed possible that rheumatoid lung disease could also be associated with an imbalance of T-lymphocyte subpopulations. To test this hypothesis, patients with chronic interstitial lung disease and RA were evaluated by lung biopsy, gallium-67 scanning and bronchoalveolar lavage to assess the activity of the lung disorder and the T-lymphocyte subpopulations were identified with the OKT4, OKT8 and Tec T-5.9 monoclonal antibodies. The Tec T-5.9 is a recently described monoclonal antibody which recognizes a small T-cell fraction of the OKT4 positive T-lymphocytes, responsible for many helper T-cell functions, including the response to allogenic antigens and help in immunoglobulin production by B-cells. Histologic evaluation of the biopsies demonstrated active lung inflammation in all patients and gallium-67 scans showed an increased lung uptake in five of the six patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗