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Biomedical subjects

F Gervasi

Publications and source records attributed to F Gervasi.

24 records · Page 2Linked to original sources

In vitro impairment of interleukin-5 production in HLA-B8, DR3-positive individuals implications for immunoglobulin A synthesis dysfunction.

Healthy subjects carrying the HLA-B8,DR3 haplotype may show a large number of immune dysfunctions. Concerning T-cell dysfunctions, the most intriguing is a defect of the early phases of T-cell activation, responsible for the impairment of in vitro mitogen-stimulated cytokine production. Regarding B-cell dysfunctions, one the most fascinating topics is the association between this haplotype and IgA deficiency in healthy blood donors. Accordingly, HLA-B8,DR3-positive healthy subjects show significantly lower values of serum IgA than HLA-B8,DR3-negative ones. Because IL-5 is a stimulating factor for the secretion of IgA by committed B cells, we have analyzed the in vitro mitogen-stimulated IL-5 production by MNCs from healthy HLA-B8,DR3-positive individuals to study whether they display an impaired production of IL-5. The results clearly demonstrate that MNCs from HLA-B8,DR3-positive individuals display significant reduction of IL-5 production, suggesting that IgA synthesis dysregulation observed in HLA-B8,DR3-positive subjects could be due to an impairment of IL-5 production.

Adult↗

IL-4 is essential for the systemic transfer of delayed hypersensitivity by T cell lines. Role of gamma/delta cells.

Hapten (trinitrophenyl)-specific T cell lines were obtained by repeated stimulation of lymph node cells from immune mice with Ag in vitro. These T cell lines show phenotypic properties and a pattern of cytokine production typical of Th1 cells and consisted of more than 90% V beta 8.2+ T lymphocytes and 6 to 9% gamma/delta + T lymphocytes. The lines mediate a local passive transfer of DTH when injected at the site of Ag challenge but fail to mediate a systemic passive transfer of DTH when injected i.v. However, a successful systemic passive transfer of DTH was observed when IL-4 was given to recipient mice together with the T cell lines or when the T cell lines were incubated in vitro with IL-4. IL-4 enables systemic, specific passive transfer of DTH at a dose of 10 pg/ml in vitro and at a dose of 10 pg/mouse in vivo; it is effective when injected 4 h before cell transfer but not when given 1 to 5 days earlier. Cytofluorimetric analysis shows that the gamma/delta + cells and not the V beta 8.2+ cells of the line express IL-4R and a good systemic transfer of DTH is observed when gamma/delta + cells are incubated in vitro with IL-4 and then injected together with V beta 8.2+ cells into recipient mice. In contrast, injection of V beta 8.2+ cells treated with IL-4 together with gamma/delta + cells fails to transfer DTH. Overall, the present results show that IL-4 is an important mediator in the DTH reaction and that gamma/delta + cells are one of the targets of its action.

Animals↗

In vitro cytokine production by HLA-B8,DR3 positive subjects.

It is well known that healthy subjects carrying the HLA-B8,DR3 haplotype may show an impairment of immune system, the T cells being the most affected. To gain insight into the mechanism(s) of the impairment displayed by these subjects, efforts have been centered on the study of in vitro cytokine production because of the pivotal role played by these mediators in the activation and control of several immune functions. The available results indicate that the ability to several immune functions. The available results indicate that the ability to produce interleukin-1 (IL-1), IL-2 and the soluble form of its receptor (sIL-2R) is impaired in HLA-B8,DR3 positive healthy subjects. To better characterize the cytokine production capacity of HLA-B8,DR3 positive subjects, we have investigated the pattern of in vitro production of IL-2, sIL-2R, IL-4. IL-6 and gamma-interferon (gamma-IFN) by mononuclear cells from HLA-B8, DR3 positive subjects after phytohaemoagglutinin stimulation. A significant decrease of IL-2, sIL-2R and gamma-IFN production by HLA-B8,DR3 positive subjects was observed. No significant difference was instead found between the HLA-B8,DR3 positive subjects and the negative ones as regards IL-4 and IL-6 production. We suggest that this imbalanced cytokine production may well account for the pattern of immune response that may observed in HLA-B8,DR3 positive subjects, i.e. a normal or increased humoral response in face of a low T cell immune responsiveness.

Adult↗

Correlation between clinical response and urinary interleukin levels using different doses and intravesical administration schedules of interferon-alpha-2b combined with epirubicin: a pilot study.

A total of 62 patients at high risk for recurrence of superficial bladder cancer were selected for a study designed to compare the prophylactic efficacy of different doses and schedules of sequential intravesical instillations of epirubicin and interferon-alpha-2b and to evaluate which sequence could enhance the release of cytokines in the urine. Our investigations showed a significant increase in urinary concentrations of interleukins in patients who received the sequential intravesical administration of epirubicin and interferon-alpha-2b. Higher urinary concentrations of interleukins and a lower recurrence rate were detected in patients who received interferon-alpha-2b 24h after epirubicin instillation.

Administration, Intravesical↗

Induction of contact sensitivity by cell-associated immunocomplexes requires activation of the early complement components.

Lymph node cells collected from CBA/J mice 4 days after painting the skin with picryl chloride behave like antigen presenting cells and induce contact sensitivity when injected into naive recipient mice. The immunizing capacity of these '4-day' cells is due to T cells which carry on their membrane hapten-IgM immunocomplexes. Incubation of the cells with complement from mouse strains that express high C4 serum levels (C4H), abolishes their immunizing capacity. This effect is related to the activation of the early components of the classical complement pathway, as supported by experiments using C3 and C4-depleted or C5 and C6-genetically deficient mouse sera. The detection of different amounts of C3b and C4b on the surface of 4-day T cells after incubation with C4L and C4H sera supports the possibility that membrane bound activated complement components could modify the immunizing capacity of these cells. Results herein reported suggest that membrane-bound C3b and C4b are not per se inhibitory but interfere with the residual complement activating capacity of 4-day T cells. The role of complement activation by 4-day T cells is pivotal as complement depletion of recipient mice by cobra venom factor (CVF) inhibits the immunizing capacity of untreated 4-day T cells, while 4-day T cells treated with complement in vitro and injected together with C4a anaphylatoxin are able to immunize recipient mice.

Animals↗