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Biomedical subjects

G Del Prete

Publications and source records attributed to G Del Prete.

At least 37 records · Page 2Linked to original sources
PubMed1997

T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease.

Chronic antral gastritis following Helicobacter pylori (Hp) infection is characterized by a cellular inflammatory infiltrate whose cytokines may represent a host-dependent factor influencing the outcome of the infection. The pattern of cytokines produced by the immunologically active cells in the gastric antrum was analyzed at the mRNA level in antral biopsies from five Hp-infected patients with duodenal ulcer and three Hp-negative dyspeptic controls. T cell clones were generated from parallel antral biopsies of the same Hp-infected patients and assessed for reactivity to Hp Ags, cytokine profile, and effector functions. Antral biopsies from all Hp-infected patients showed IFN-gamma, TNF-alpha, and IL-12, but not IL-4, mRNA expression, whereas no cytokine mRNA signal was found in the mucosa of controls. A total of 24 out of the 163 CD4+ T cell clones (15%) derived from Hp-infected patients proliferated in response to a Hp lysate; 11 clones (46%) also reacted with Cag-A, 2 with Vac-A, and 1 with urease. Upon Ag stimulation, 20 out of the 24 Hp-reactive clones (83%) produced IFN-gamma, but not IL-4 or IL-5 (Th1-like), whereas 4 produced IFN-gamma, IL-4, and IL-5 (Th0-like). All Hp-specific clones secreted high levels of TNF-alpha. At low T:B cell ratio, Hp-specific clones expressed Ag-dependent helper function for B cell proliferation and Ig production, whereas at higher T:B cell ratios, 15 Th1 and 2 Th0 clones lysed Ag-pulsed autologous EBV-transformed B cells. Results provide evidence for Hp-specific Th1 effectors in the gastric antrum of Hp-infected patients, where they may play a role in the genesis of either peptic ulcer or Hp-associated gastric B cell lymphoma.

Adult↗
PubMed1997

Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer.

Helicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp-induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T cell clones derived from six Hp-infected patients with chronic gastritis and peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin-associated protein (CagA). In contrast, 34 (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin-4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.

Adult↗
PubMed1997

Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B.

The cytokine pattern secreted by T cells on viral antigen recognition is believed to exert a profound influence on both the type of disease caused by the infecting agent and the final outcome of the viral infection. To characterize the cytokine pattern associated with spontaneous resolution of acute hepatitis B, we analyzed interferon gamma (IFN-gamma), interleukin (IL)-4, and IL-5 production by a wide series of hepatitis B virus (HBV) nucleocapsid-specific T-cell lines (34 lines) and T-cell clones (71 clones) derived from the peripheral blood of 13 patients during the acute or recovery phase of hepatitis B (2 and 7 of them were studied only in the recovery or the acute phase, respectively, and 4 during both). Most T-cell lines (67%) and clones (77%) isolated during the acute phase of infection expressed a T-helper (Th) 1 cytokine profile dominated by the production of IFN-gamma. A larger proportion (74%) of T-cell lines produced several years after resolution of hepatitis was able to secrete not only IFN-gamma, but also IL-4 and IL-5 (Th0-like cells). Results indicate that the antigen-specific fraction of peripheral blood T cells in acute self-limited hepatitis B selectively secrete Th1-type eytokines, suggesting that Th1-mediated effects may contribute not only to liver cell injury, but probably also to recovery from disease and successful control of infection.

Acute Disease↗
PubMed1997

Uncoupling of T-cell antigen receptor and downstream protein tyrosine kinases in common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestations of the disease and the underlying mechanisms leading to the immunodeficiency. Although the overt defect is an impairment in B-cell function, there is increasing evidence of primary T-cell dysfunctions in a proportion of patients with CVID. We have analyzed T-cells from six CVID patients for activation of both early and late events in response to TCR triggering. The data showed that T-cells from three of six CVID patients were defective in the capacity to initiate the TCR/CD3 signaling pathway by activating intracellular tyrosine kinases, associated with impaired proliferative responses to TCR/CD3 triggering. Since both surface expression of the TCR/CD3 complex and intracellular expression of key tyrosine kinases such as p56lek and ZAP-70 were normal in these patients, our data suggest a defect in the earliest step of TCR signal transduction.

Adult↗
PubMed1997

Different cytokine profiles of intraphepatic T cells in chronic hepatitis B and hepatitis C virus infections.

BACKGROUND & AIMS: The cytokine pattern secreted by T cells at the site of viral replication may influence the final outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. The aim of this study was to assess whether a cytokine imbalance oriented toward T helper (Th) 1 or Th2-type responses may play a role in chronic hepatitis B or C. METHODS: Production of interferon (IFN)-gamma, interleukin (IL)-4, and IL-5 by wide series of T-cell clones derived from the liver of 6 patients with chronic hepatitis B (291 clones) and 9 patients with chronic hepatitis C (260 clones) was studied. T-cell clones were generated by limiting dilution from freshly isolated mononuclear cells derived from liver tissue to give a reliable representation of the intrahepatic inflammatory infiltrates. RESULTS: The majority of liver-infiltrating T cells in chronic hepatitis C were Th1 cells able to secrete IFN-gamma but unable to secrete IL-4 or IL-5, whereas in hepatitis B, most CD4+ and CD8+ liver T cells were ThO-like cells able to produce not only IFN-gamma but also IL-4 and IL-5. CONCLUSIONS: The different cytokine profiles of T cells within the liver in chronic HBV and HCV infections illustrate a different behavior of the local immune response in these two infections that may have pathogenetic implications.

Adult↗
PubMed1996

Long-lasting memory T cell responses following self-limited acute hepatitis B.

The molecular and cellular basis of long-term T cell memory against viral antigens is still largely undefined. To characterize anti-viral protection by memory T cells against non-cytopathic viruses able to cause acute self-limited and chronic infections, such as the hepatitis B virus (HBV), we studied HLA class II restricted responses against HBV structural antigens in 17 patients with acute hepatitis B, during the acute stage of infection and 2.2 to 13 yr after clinical resolution of disease. Results indicate that: (a) significant T cell proliferative responses to HBV nucleocapsid antigens were detectable in all patients during the acute phase of infection and in 14/17 also 2-13 yr after clinical resolution of disease; b) long-lasting T cell responses were sustained by CD45RO+T cells, predominantly expressing the phenotype of recently activated cells; c) limiting dilution analysis showed that in some patients the frequency of HBV-specific T cells was comparable to that observed in the acute stage of infection and, usually, higher than in patients with chronic HBV infection; d) the same amino acid sequences were recognized by T cells in the acute and recovery phases of infection; and e) HBV-DNA was detectable by nested-PCR in approximately half of the subjects. to conclusion, our results show that vigorous anti-viral T cell responses are detectable in vitro several years after clinical recovery from acute hepatitis B. Detection of minute amounts of virus in some recovered subjects suggests that long-term maintenance of an active anti-viral T cell response could be important not only for protection against reinfection but also for keeping the persisting virus under tight control.

Acute Disease↗
PubMed1996

CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: evidence for a T helper 2-mediated condition.

Omenn's syndrome (OS) is a severe immunodeficiency, characterized by clinical and laboratory features reminiscent of a T helper type-2 (Th2) response. CD30, a member of the tumor necrosis factor receptor superfamily, has been found to be preferentially expressed by human T cell clones exhibiting a Th2-line profile and function. We investigated whether there are derangement in CD30 expression in tissues, and/or abnormalities in soluble CD30 (sCD30) levels in the serum, or both, of three children with OS and one child with maternal engraftment and Omenn's-like syndrome (OLS). Large proportions of tissue-infiltrating T lymphocytes from all four patients expressed CD30, whereas in control tissues, including peripheral blood, CD30+ T lymphocytes were extremely few or absent. In addition, levels of sCD30 were abnormally increased in all patients' sera. T cell clones were generated from sorted CD30+ and CD30-peripheral blood T cells of the patient with OLS who showed unusually high numbers of circulating CD30+ T lymphocytes. Most CD4+ T cell clones derived from CD30+ cells showed a Th2-like cytokine profile, whereas the majority of clones generated from CD30-T cells were Th1. These findings support the hypothesis that Th2 cells are involved in the pathogenesis of OS. Moreover, they provide evidence that detection of CD30+ T cells in tissues, increased levels of sCD30 in biological fluids, or both, reflect the presence of immune responses characterized by prevalent activation of T cells producing Th2 cytokines.

Cytokines↗
PubMed1996

Immune mechanisms in the pathogenesis of inflammatory gastrointestinal disorders.

The cytokine secretion profile of T cells present in the gastric antrum of Helicobacter pylori-infected patients with peptic ulcer and in the gut of patients with Crohn's disease was investigated. A type 1 T helper (Th1)-dominated response was detected in the gastric antrum of Helicobacter pylori-infected subjects with peptic ulcer by both reverse transcriptase-PCR and immunohistochemistry. By using a T-cell cloning technique, it was shown that the majority of Th 1 cells were specific for Hp antigens. A Th1 predominance, which associated with high IL-12 expression, was also found, at both clonal and immunohistochemical level, in the gut of patients with Crohn's disease. These findings suggest that the Th1/Th2 paradigm may be useful to explain the inflammatory reactions involved in the pathogenesis of some gastrointestinal disorders.

Crohn Disease↗
PubMed1996

Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis.

BACKGROUND: An increased number of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. OBJECTIVE: To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. METHODS: We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in 11 subjects with chronic bronchitis examined during an exacerbation. The findings were compared with those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells (tryptase), and T-lymphocytes (CD3) in the submucosa. RESULTS: As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of chronic bronchitis (P < 0.001), whereas the number of IL-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No differences were observed in the number of mast cells and T-lymphocytes between the four groups of subjects examined. CONCLUSIONS: This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of chronic bronchitis, but only in asthma is it associated with an increased expression of IL-5 protein in the bronchial mucosa.

Adult↗
PubMed1995

CD30-mediated signaling promotes the development of human T helper type 2-like T cells.

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.

Antigen-Presenting Cells↗
PubMed1995

Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes.

The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1 cytokine profile, but none of seven Th2 clones, induced TF production and PCA. T-cell blasts from four Th1 activated clones were fixed with paraformaldehyde and added to monocytes in the presence of medium alone or their supernatants. Addition of either fixed Th1 cells or their supernatants induced low TF production (0.2 to 0.6 ng/mL), whereas addition of both resulted in much higher TF synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only interferon-gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4 ng/mL). No TF synthesis was induced by activated and fixed Th2 cells and/or their supernatants, whereas combined addition of fixed Th2 cells and Th1 supernatants or IFN-gamma induced noticeable TF production. The addition of either anti-IFN-gamma antibody or Th2 supernatants to monocytes stimulated with activated and fixed Th1 cells plus their supernatant resulted in a dose-dependent inhibition of TF synthesis, which was partially restored by neutralization of interleukin-4 (IL-4) or IL-10. Addition of recombinant IL-4, IL-13, or IL-10, but not IL-5, inhibited the Th1-induced TF production by monocytes. Data indicate that both CD8+ and CD4+ Th1, but not Th2, T cells can help TF production and PCA. Both cell-to-cell contact with activated T cells and Th1-type cytokines, in particular IFN-gamma, are required for optimal TF synthesis, whereas Th2-derived cytokines (IL-4, IL-13, and IL-10) are inhibitory. This may be of potential interest for future therapeutic strategies.

Antigens↗
PubMed1995

CD30 and type 2 T helper (Th2) responses.

CD30 is one of the members of the tumor necrosis factor receptor superfamily, originally described as a marker of Reed-Sternberg and Hodgkin's cells in Hodgkin's lymphoma. CD30 appears to be preferentially expressed on, and its soluble form (sCD30) released by, CD4+ and CD8+ T cell clones capable of producing T helper 2 (Th2)-type cytokines. In noneoplastic conditions, CD30+ T cells are barely detectable in vivo; however, a few allergen-specific CD4+CD30+ T cells inducible to the production of Th2-type cytokines could be sorted out from the circulation of allergic subjects after allergen exposure. Moreover, high numbers of CD30+ T cells were found in the lymph node of a patient suffering from Omenn's syndrome, a rare congenital Th2-mediated immunodeficiency disorder. More importantly, high serum levels of sCD30 were observed in some conditions in which a pathogenetic role for Th2 cells has been suggested, such as Omenn's syndrome, atopy, systemic lupus erythematosus, and after infection with measles virus or human immunodeficiency virus. Thus, detection of CD30+ T cells and/or of increased levels of sCD30 may reflect the presence of immune responses or immune alterations characterized by the prevalent activation of Th2-like cells.

HIV Infections↗
PubMed1995

Hepatitis C virus infection of mononuclear cells from peripheral blood and liver infiltrates in chronically infected patients.

The mechanisms underlying chronicity of hepatitis C virus (HCV) infection are poorly understood, but the importance of impaired viral clearance by the immune system has been suggested. The prevalence of HCV infection of peripheral blood mononuclear cells (PBMC) was in investigated in 34 persistently infected patients with anti-HCV (7 with liver cirrhosis, 10 with chronic active hepatitis, 5 with chronic persistent hepatitis, 4 with chronic lobular hepatitis, and 8 healthy carriers) by polymerase chain reaction (PCR). HCV infection of 116 T cell clones derived from liver infiltrating mononuclear cells obtained from 3 patients with chronic liver disease was examined using the same methods. HCV genomic sequences were found in fresh, unstimulated PBMC from 20 patients with cirrhosis, and chronic active and persistent hepatitis, but in none of the healthy carriers and only in mitogen-activated cells from 1 out of 4 patients with autoresolving chronic lobular hepatitis. Active PBMC infection was confirmed by identification of anti-genomic HCV sequences in the majority of HCV RNA-positive cells (fresh or mitogen-stimulated). A high percentage of T cell clones obtained from liver infiltrates were found to be infected by HCV. These findings suggest that HCV infection of lymphatic cells plays a role in the pathogenesis of chronically evolving liver damage. PBMC may represent a reservoir for latent infection and a site for viral multiplication.

Alanine Transaminase↗
PubMed1995

CD30, Th2 cytokines and HIV infection: a complex and fascinating link.

CD30 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily, and was originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. CD30 is preferentially expressed on CD4+ and CD8+ T-cell clones that produce T helper 2 (Th2)-type cytokines, and is also released in a soluble form by these cells. Elevated serum levels of soluble (s)CD30 have been found in some conditions in which a pathogenic role for Th2 cells has been suggested, such as atopy, Omenn's syndrome, systemic lupus erythematosus, as well as following infection with measles virus or human immuno-deficiency virus (HIV). Here, Gianfranco Del Prete and colleagues suggest a complex and fascinating link between the expression and release of CD30, and the immunopathogenesis of HIV infection.

Cytokines↗
PubMed1995

Preferential expression of CD30 by human CD4+ T cells producing Th2-type cytokines.

A large panel of human CD4+ T helper (Th) cell clones with established Th1, Th2, or Th0 profiles of cytokine secretion were examined for the expression of CD30, a member of the tumor necrosis factor receptor superfamily. Th1 clones expressed poor or no CD30 mRNA, and showed low or undetectable expression of both membrane and soluble CD30 (sCD30) protein, whereas Th2 clones showed both CD30 mRNA and membrane CD30 and released substantial amounts of sCD30. Th0 clones exhibited an intermediate pattern of CD30 expression and release. When T cells from the same donor were stimulated with three different antigens (purified protein derivative, PPD; Toxocara canis excretory/secretory antigen, TES; Lolium perenne group I, Lol p I), production of high concentrations of IFN-gamma, but not expression of CD30 or production of IL-4 and IL-5, were observed at any time after stimulation with PPD. In contrast, both CD30 expression and production of IL-4 and IL-5, but not of IFN-gamma, were concomitantly detectable in TES- and Lol p I-reactive T cells, suggesting a temporal relationship between CD30 expression and beginning of Th2-type cytokine production. Finally, CD4+CD30+ T cells specific for Lol p I and inducible to production of Th2-type cytokines were sorted out from the circulation of grass-sensitive patients in concomitance with the onset of allergic symptoms during the seasonal exposure to grass pollen. Thus, CD30 expression appears to be associated with the differentiation/activation pathway of human T cells producing Th2-type cytokines.

Allergens↗
PubMed1994

Polyclonal B cell activation induced by herpesvirus saimiri-transformed human CD4+ T cell clones. Role for membrane TNF-alpha/TNF-alpha receptors and CD2/CD58 interactions.

We have shown that in vitro infection herpesvirus saimiri (HVS) can transform human CD4+ T cell clones with defined Th1 or Th2 cytokine profiles to continuous growth. We report here that transformation with HVS enabled both Th1 and Th2 clones to stimulate proliferation and Ig production by autologous or allogeneic B cells in the absence of stimulants. The polyclonal B cell-activating property of HVS-transformed clones was not related to free virus or soluble cytokines, but rather was dependent on an Ag-nonspecific, MHC-unrestricted, contact-dependent mechanism. T blasts from unstimulated HVS-transformed clones did not express CD40 ligand (CD40L) mRNA or CD40L protein, whereas a proportion of them constitutively expressed membrane TNF (mTNF)-alpha. Both CD40L and mTNF-alpha were detectable on either uninfected or HVS-transformed clones upon mitogen stimulation. The activation of high-density B cells by unstimulated HVS-transformed clones was not inhibited by soluble CD40-Ig fusion protein, but was strongly reduced by either anti-TNF-alpha or anti-TNF-alpha receptor (TNF-alpha R) mAbs. Addition of anti-CD2 and/or anti-CD58 mAbs was also inhibitory, but no additive effect with anti-TNF-alpha and/or anti-TNF-alpha R mAbs was observed. Neither anti-IL-2 nor CD40-Ig inhibited the proliferation of naive IgD+ B cells cocultured with fixed unstimulated HVS-transformed clones, whereas a combination of anti-TNF-alpha and anti-TNF-alpha R mAbs was inhibitory. In addition, fixed unstimulated HVS-transformed clones induced Ig synthesis in IgD+ naive B cells even in the absence of exogenous IL-2. Data suggest that both the mTNF-alpha/TNF-alpha R and the CD2/CD58 pathways, but not the CD40L-CD40 interaction plus secreted cytokines, are involved in the unusual mode of B cell activation exerted by CD4+ HVS-transformed clones.

Antibodies, Monoclonal↗