Search PubMed⌕ Search

Biomedical subjects

L Trentin

Publications and source records attributed to L Trentin.

At least 73 records · Page 4Linked to original sources
PubMed1993

Expression and functional role of tumor necrosis factor receptors on leukemic cells from patients with type B chronic lymphoproliferative disorders.

Two receptors for tumor necrosis factor (TNF) with different molecular weight (75-Kd and 55-Kd) and binding affinity have been recently discovered. To investigate the distribution and the functional role of these receptors on leukemic B cells from hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia (B-CLL) patients, we evaluated: (1) the cytofluorimetric pattern of uncultured and cultured leukemic B cells incubated with utr-1 and htr-9 monoclonal antibodies (MoAbs), which specifically recognize the 75-Kd and 55-Kd TNF receptors (TNFR), respectively; (2) the effect of TNF-alpha and TNF-beta on leukemic B cells in an in vitro proliferation assay; (3) the role of anti-TNFR MoAbs on TNF-alpha and TNF-beta-driven B-cell growth; and (4) the proliferative effect of utr-1 and htr-9 MoAbs on in vitro cultured leukemic cells. Our study shows that the high affinity (75-Kd) but not the low affinity (55-Kd) TNFR molecules are expressed on freshly isolated leukemic B cells recovered from HCL and B-CLL patients. The expression of these receptors was neither upregulated nor downregulated by different stimuli, including TNF-alpha, TNF-beta, B-cell growth factor, and interleukin-2. TNF-alpha efficiently triggers the proliferation of HC and, to a lesser extent, the growth of B-CLL cells. TNF-beta was also able to transduce the proliferative signal in HCL, but not in B-CLL patients. TNF-alpha- and TNF-beta-driven B-cell proliferation was inhibited by the preincubation of leukemic B cells with utr-1 but not htr-9 MoAb. Moreover, anti-75-Kd, but not anti-55-Kd TNFR MoAb, was able to trigger the proliferation of leukemic B cells, and in particular of HC. These results show that leukemic B cells from patients with HCL and B-CLL are equipped with a fully functional high affinity TNFR.

Aged↗
PubMed1993

CD8 alveolitis in sarcoidosis: incidence, phenotypic characteristics, and clinical features.

PURPOSE: Although the accumulation of CD4 cells in the lung and other involved tissues is regarded as the distinctive immunologic feature of sarcoidosis, a few sarcoid patients can present with CD8 alveolitis. This study evaluates the incidence as well as the clinical and immunologic features of sarcoidosis presenting with CD8 alveolitis. PATIENTS AND METHODS: A total of 2,214 consecutive bronchoalveolar lavage (BAL) specimens obtained from 481 patients with sarcoidosis between January 1985 and December 1991 were retrospectively analyzed. Subjects who entered the study had the following characteristics: (1) lymphocyte alveolitis and (2) lung CD4/CD8 ratio less than 1.0. Only data obtained from patients with a first episode of pulmonary involvement were included in the analysis (394 patients). RESULTS: Fifteen of the 394 patients studied at the time of diagnosis showed CD8 alveolitis as the presenting manifestation; the incidence of this phenomenon was 3.8%. A follow-up study of BAL T-cell subsets demonstrated that patients who showed high-intensity CD8 alveolitis at the onset of the disease maintained the CD8 pattern of alveolitis during relapses. Phenotypic analysis of lung T cells revealed that the accumulation of CD8 lymphocytes was due to the discrete local increase of CD45RO+ "memory" cells equipped with a number of accessory structures, including adhesion molecules and class II major histocompatibility complex-related HLA-DR antigen. CONCLUSIONS: The accumulation of CD8 cells in the sarcoid lung is likely to reflect a homing of memory cells due to the ongoing immunologic response against the unknown antigen causing the disease. Although CD8 alveolitis can be considered a relatively rare event in sarcoidosis, the possibility that an increase of CD8 cells in the BAL fluid might be sustained by an underlying sarcoid inflammatory process should never be dismissed on clinical grounds in patients with interstitial lung disease.

Adult↗
PubMed1993

Pulmonary immune cells in health and disease: lymphocytes.

Immunological defence mechanisms of the lung are provided by several different types of immunocompetent cell. Among these, the most important are lymphocytes, alveolar macrophages and neutrophils. This review focuses mainly on the pattern of physiological activities of pulmonary lymphocytes in the local host defences. The article provides an overview of the events leading to the recruitment, homing and activity of lymphocytes in the lower respiratory tract. The pathways through which the pulmonary lymphoid system recognizes, destroys and contributes to removing potentially harmful inhaled antigenic materials are also briefly discussed. The final section of the article highlights the pathogenetic role envisaged for lymphoid cells in disease states, in the context of the known biology of these cells.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Release of granulocyte-macrophage colony-stimulating factor by alveolar macrophages in the lung of HIV-1-infected patients. A mechanism accounting for macrophage and neutrophil accumulation.

In this paper, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lung of patients with HIV-1 infection was evaluated. This cytokine has well recognized effects on granulocyte and macrophage growth and differentiation and plays some role in the mechanisms leading to the accumulation of alveolar macrophages (AM) in patients with interstitial lung disease. Detectable levels of GM-CSF (up to 10 pg/ml) were demonstrated in unconcentrated bronchoalveolar lavage fluid retrieved from HIV-1-seropositive patients, thus suggesting that the GM-CSF is released in vivo in the lung during HIV-1 infection. A statistically significant correlation was demonstrated between the bronchoalveolar lavage concentrations of GM-CSF and the absolute numbers of AM and lung neutrophils. Cell-free supernatants obtained from unstimulated 24-h cultured AM isolated from HIV-1-infected patients contained discrete amounts of GM-CSF, as demonstrated by an immunoenzymatic assay. AM lost the capability of releasing GM-CSF after 72 h of culture, thus suggesting that the production of GM-CSF is not constitutive in AM. After exposition of AM with LPS, the release of GM-CSF and the expression of its mRNA significantly increased with respect to the baseline values; interestingly, the amount of GM-CSF released by LPS-stimulated AM was more than 10-fold higher in HIV-1-infected patients than in healthy subjects. As demonstrated by flow cytometry analysis, more than 70% of freshly isolated AM efficiently bound phycoerythrin-GM-CSF, thus indicating that they express the receptor for GM-CSF. Determination of AM in G1, S, and G2+M by flow cytometry showed that, after 48 h of culture with GM-CSF, 5.5 to 7% of AM entered the proliferative phase of the cell cycle. Taken together, these findings suggest that AM might represent an important source of GM-CSF production in HIV-1 infection. In particular, the hypothesis is formulated that pulmonary opportunists might trigger AM to synthesize GM-CSF in situ. The local overproduction of this cytokine is likely to play a role in the pathogenic events leading to the local proliferation of AM and recruitment of neutrophils in AIDS-associated interstitial lung disease.

AIDS-Related Complex↗
PubMed1992

Role of tumor necrosis factor-alpha and its specific 55-Kd and 75-Kd receptors in patients with lymphoproliferative disease of granular lymphocytes.

The role of tumor necrosis factor-alpha (TNF-alpha) in the development of in vitro proliferative and cytotoxic abilities of granular lymphocytes (GL) in patients with lymphoproliferative disease of GL (LDGL) has been investigated. To this aim, taking advantage of the recent generation of specific monoclonal antibodies (MoAbs) reacting with the p55 and p75 TNF receptors (TNF-R) (htr-9 and utr-1 MoAb, respectively), we evaluated the expression and the functional role of each TNF-R in freshly isolated highly purified GL from a series of 10 LDGL patients (six CD3+ T-lineage GL and four CD3- natural killer [NK]-lineage GL). The expression of TNF-alpha transcripts and the release of TNF-alpha in the culture medium at resting conditions and following cell activation were also studied. Our data indicate that at resting conditions both CD3+ and CD3- GL express only the p75 TNF-R. Accordingly, a specific inhibition of phycoerythrin (PE)-conjugated TNF-alpha binding was demonstrated by the anti-p75 TNF-R utr-1 MoAb, but not by the anti-p55 htr-9 MoAb. Following activation with interleukin-2 (IL-2), anti-CD3, or anti-CD16 MoAbs, an increased expression of the p75 TNF-R and a slight induction of the p55 TNF-R was observed. Weak expression of specific TNF-alpha transcripts was detected at resting conditions and on unstimulated cells, whereas both IL-2 or anti-CD3 MoAb induced TNF-alpha mRNA. Under these in vitro conditions, detectable amounts of this cytokine were demonstrated in the culture supernatant of GL. The cytotoxic and proliferating activities mediated by IL-2 or anti-CD3 MoAb were dampened by anti-TNF-alpha antibody, suggesting a role for endogenous TNF-alpha in these functions. Both utr-1 and htr-9 MoAbs showed a moderate inhibition of proliferative activity, whereas cytotoxicity was not reduced. Taken together, our results suggest that TNF-alpha plays a role in the mechanisms leading to CD3+ and CD3- GL in vitro activation in patients with LDGL.

Aged↗
PubMed1992

Expression and functional role of the p75 interleukin 2 receptor chain on leukemic hairy cells.

Hairy cell leukemia is a chronic lymphoproliferative disorder characterized by the expansion of neoplastic B-cells expressing the p55 chain of the interleukin 2 receptor (IL-2R) system that is recognized by anti-CD25 monoclonal antibodies (mAb) and binds interleukin 2 (IL-2) with low affinity. In the present study we investigated leukemic hairy cells (HC) for the presence of the p75 IL-2R chain which binds IL-2 with intermediate affinity and plays a crucial role in transducing the message to the cell. For this purpose, we tested highly enriched leukemic HC from six hairy cell leukemia patients for the presence of IL-2R transcripts and for the expression of the p55 and p75 IL-2R chains on their surface membrane by flow cytometry and immunoprecipitation analyses. The functional role of IL-2 in the regulation of HC proliferation was also investigated. Our results indicate that freshly isolated HC express detectable messages for both the p75 IL-2R and the p55 IL-2R. Flow cytometry analysis demonstrated detectable levels of p75 IL-2R on the HC from all patients tested. A mixture of two specific mAb was able to immunoprecipitate detectable amounts of p75 IL-2R from leukemic HC. When leukemic HC were cultured in the presence of several concentrations of IL-2 a low proliferative response was observed. Moreover, the IL-2-driven proliferation of HC was markedly inhibited by anti-p75 IL-2R mAb and to a lesser extent by anti-p55 IL-2R mAb. These findings provide direct evidence of the expression of different IL-2 receptors on leukemic HC and suggest that these molecules might play a role in leukemic cell growth.

Adult↗
PubMed1992

Cytotoxic in vitro function in patients with metastatic renal cell carcinoma before and after alpha-2b-interferon therapy. Effects of activation with recombinant interleukin-2.

In this study the characteristics of the cytotoxic function in a series of patients with metastatic renal cell carcinoma (RCC) were analyzed and the possibility of modulating this capacity in vitro with the use of biologic response modifiers (BMR) such as alpha-interferon (alpha-IFN) and recombinant interleukin-2 (rIL-2) was verified, with the ultimate goal of providing a rationale for a therapeutic approach to this disease with these molecules. Peripheral blood mononuclear cells (PBMC) of patients with advanced RCC were tested for natural killer (NK) and lymphokine-activated killer (LAK) activity both before and after alpha-IFN therapy. In addition, surface markers of unstimulated and stimulated cells were analyzed and in vitro assays were performed to determine the proliferative capacity in response to the stimulus with rIL-2. During an evaluation before treatment, defective NK activity was observed that could be corrected by incubating the cells with rIL-2. In these subjects, LAK cells could be consistently generated after PBMC were activated with this cytokine in vitro. No changes in NK and LAK activity were found after alpha-IFN therapy. In contrast, treatment with alpha-IFN affected the proliferative response of PBMC to rIL-2, and a significant decrease in this in vitro capacity was observed during follow-up. The ability to restore NK activity and obtain an adequate LAK cytotoxicity from the PBMC of patients with RCC supports a therapeutic approach with BRM. However, the fact that this type of treatment affects the proliferative response of PBMC to rIL-2 must be considered when clinical trials are designed for patients with RCC.

Adult↗
PubMed1992

Expression of cell adhesion molecules in human melanoma cell lines and their role in cytotoxicity mediated by tumor-infiltrating lymphocytes.

The role of cell adhesion molecules (CAM) LFA1, ICAM-1, LFA3, VLA1, VLA4, CD29, CD44, and CD56 in tumor-infiltrating lymphocyte (TIL) and natural killer cell (NK)-mediated killing of target cells was studied. Melanoma cell lines and autologous TIL were derived from seven patients with metastatic melanoma, and cytotoxicity assays were done in the presence and absence of monoclonal antibodies (MoAb) to CAM expressed on melanoma cells or TIL. The melanoma cell lines analyzed were all positive for CD29 and LFA3 expression, negative for LFA1 expression, but showed variable expression of ICAM-1, VLA1, VLA4, CD44, and CD56. The effects of anti-CAM antibodies on TIL-mediated melanoma killing fell into three categories: (1) consistent inhibition of TIL-mediated killing was observed when melanoma cells were pretreated with anti-ICAM1 and anti-LFA-3 MoAb or when TIL were pretreated with anti-LFA1; (2) no effect was observed when melanoma cells were pretreated with anti-CD56; or (3) a discreet, but significant, inhibition was observed when target cells were pretreated with anti-CD29, anti-VLA1, anti-VLA4, and anti-CD44. Cytotoxicity was significantly enhanced by pretreatment of target cells with gamma-interferon (gamma-IFN), although gamma-IFN did not augment surface expression of the CAM studied. The NK-mediated killing of K562 cells was blocked by anti-LFA1, anti-CD18, and anti-ICAM, and partially inhibited by anti-CD44 MoAb. Together, these results suggest that several accessory CAM may play a role in regulating cellular cytotoxicity. Because cytotoxicity generally correlated with the level of expression of CAM in melanoma cells, weak CAM surface expression may provide a means for melanomas to escape immune surveillance.

Antibodies, Monoclonal↗
PubMed1992

Expression of a functional p75 interleukin-2 receptor on lung lymphocytes from patients with human immunodeficiency virus type 1 (HIV-1) infection.

Lung involvement in patients affected by HIV-1 infection is characterized by an alveolitis sustained by the accumulation of CD8+ T lymphocytes. To investigate whether in situ T cell growth plays a relevant role in the pooling of CD8+ lymphocytes, we have analyzed the activity of two lymphokines involved in the mechanisms of T cell proliferation, i.e., interleukin-2 (IL-2) and interleukin-4. To this aim, following appropriate triggering and blocking, the expression and the functional role of IL-2 receptors (IL-2R) (both p55 and p75 chains) and IL-4 receptors have been analyzed on T lymphocytes obtained from the bronchoalveolar lavage (BAL) of 16 HIV-1+ patients. Molecular and phenotypic studies we performed demonstrated that CD8+ lymphocytes from the BAL of HIV-1 + patients strongly expressed the p75 chain of IL-2 receptor, while neither p55 mRNA nor its surface membrane product (Tac antigen) was detectable; in addition, there was no expression of IL-4 receptors. IL-2 stimulation was able to induce T cell growth in a dose-dependent manner, whereas IL-4 did not. Finally, using mAbs which specifically block the p55 or p75 IL-2R, we showed that both subunits of IL-2R were involved in the proliferative activity of lung lymphocytes. The results obtained in the present study directly demonstrate that BAL T lymphocytes of HIV-1 + patients express a fully functional IL-2 receptor apparatus, pointing to the role for this lymphokine in maintaining the alveolitis taking place in the lungs of AIDS patients.

Adult↗
PubMed1992

Phenotypic and functional characterization of cytotoxic cells derived from endomyocardial biopsies in human cardiac allografts.

This study was undertaken to characterize the phenotype and function of lymphocytes derived from endomyocardial biopsies in heart transplant patients. To this aim, tissue infiltrating lymphocytes were derived from seven heart transplant patients and were analyzed for the expression of a panel of markers, including CD3, CD4, CD8, CD16, CD56, CD45RA, CD45RO, alpha/beta and gamma/delta T cell receptor, and for their ability to lyse a series of targets, including NK-sensitive K-562 targets, NK-resistant Raji targets, donor related, and unrelated normal splenocytes. Our data show that the majority of cultured lymphocytes expressed the CD3+ phenotype and the alpha/beta T cell receptor. The CD4 and CD8 molecules were heterogeneously expressed among T cell lines tested. Concerning cytotoxic related markers, a significant percentage of cells were CD56+. The evaluation of CD45 isoforms showed that both "naive" and "memory" cells were present among heart TIL. Cytotoxic in vitro studies demonstrated that all our T cell lines showed an efficient cytotoxic machinery when tested against NK-sensitive targets. A marked lysis of donor-related splenocytes was demonstrated in all patients tested. To investigate the role of CD3 and HLA class I molecules in the cytotoxic mechanisms taking place in human heart allograft rejection mechanisms, TIL were assessed for their lytic activity against different targets in the presence of anti-CD3 and anti-HLA class I monoclonal antibodies (mAbs). Although donor-specific cytotoxicity was considerably inhibited by the anti-CD3 mAb, no inhibitory effect was displayed by this antibody on TIL-mediated cytotoxicity against donor-unrelated splenocytes. Anti-HLA class I mAb was able to inhibit both allospecific and nonallospecific cytotoxicity. These data suggest that different types of cytotoxic cells may be propagated from biopsy specimens of heart transplant patients.

Adult↗
PubMed1992

Spontaneous production of interleukin-6 by alveolar macrophages from human immunodeficiency virus type 1-infected patients.

To test the hypothesis that the lung represents a source of interleukin (IL)-6 in human immunodeficiency virus type 1 (HIV-1)-positive subjects, alveolar macrophages (AM) obtained from the bronchoalveolar lavage (BAL) fluid of 10 HIV-1-positive patients were investigated for the expression of IL-6 mRNA and the ability to release IL-6. The presence of IL-6 in BAL fluid was also investigated. It has been demonstrated that freshly recovered AM from HIV-1-positive patients show a strong IL-6 mRNA signal. The message for IL-6 increases following culture with LPS. Supernatants obtained from AM cultured in medium alone contain high amounts of IL-6; the values are three to four times higher following culture with LPS. IL-6 has also been detected in the BAL fluid from 5 of 8 HIV-1-positive patients. Results of immunoblotting analysis were consistent with those given above. These findings suggest that the lung represents a source of IL-6 production in HIV-1-infected subjects with lung disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1992

T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis.

T lymphocyte regulation of immunoglobulin production may be abnormal in some patients with common variable immunodeficiency (CVI). Phenotypic analysis of peripheral blood T lymphocytes from nine patients with CVI was conducted to examine whether an abnormal distribution could be detected in a functionally distinct T lymphocyte subpopulation. The percentage of CD8+ lymphocytes proved to be increased in some patients and decreased in others. In comparison with normal controls, many patients with CVI had reduced percentages of lymphocytes expressing both CD4 and CD45RA, a phenotype associate with naive CD4+ cells. There was no significant difference in CD4+ populations bearing CD29 or leucocyte adhesion molecule-1 (LAM-1) antigens. The pattern of gene rearrangement of the T cell antigen receptor (TCR) was studied using peripheral blood lymphocytes from these patients with CVI. Genomic DNA from freshly isolated lymphocytes as well as from selectively propagated CD4+ or CD8+ populations were examined using Southern blot analysis and a probe for the beta chain of the TCR. A polyclonal pattern of TCR gene rearrangement, without the appearance of dominant non-germline bands, was demonstrated in all patient samples. These data suggest that the T lymphocytes in patients with CVI have a polyclonal pattern of TCR rearrangement despite an abnormal distribution of T cell subpopulations in some patients.

Adult↗