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R Biagiotti

Publications and source records attributed to R Biagiotti.

At least 37 records · Page 2Linked to original sources
PubMed1996

Expression and release of LAG-3-encoded protein by human CD4+ T cells are associated with IFN-gamma production .

The lymphocyte activation gene (LAG) -3 is a member of the immunoglobulin super-family that is selectively transcribed in human activated T and NK cells. In this work, the possibility that LAG-3 expression by human CD4+ T cells was preferentially related to one or another phenotype of cytokine secretion was investigated. Surface LAG-3 expression correlated with IFN-gamma, but not IL-4, production in antigen-stimulated T cells and it was up-regulated by IL-12. Most activated CD4+ T cell clones with established Th1 or Th0 profiles of cytokine secretion expressed LAG-3 on their surface, whereas the great majority of Th2 clones showed neither surface LAG-3 nor LAG-3 mRNA expression. After activation, the majority of CD4+ T cell clones also released soluble LAG-3-related peptides, and such a release correlated positively with the production of IFN-gamma and inversely with the production of IL-4. Thus, LAG-3 expression by activated CD4+ human T cells appear to be preferentially associated with the differentiation/activation pathway leading to the production of IFN-gamma.

Antigens, CD↗
PubMed1995

Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones.

The effect of progesterone (P) on the cytokine production profile of Ag-specific human CD4+ T cell lines and clones was investigated. T cell lines specific for purified protein derivative or streptokinase (SK) derived in the presence of P exhibited significant increased ability to produce IL-5 in comparison with T cell lines derived in the absence of P. Moreover, IL-4 was significantly increased in SK-specific T cell lines derived in the presence of P in comparison with SK-specific T cell lines derived in the absence of this hormone. In addition, SK-specific T cell lines generated in the presence of P developed into T cell clones showing a Th0-, instead of Th1-like, cytokine profile. Furthermore, SK-specific T cell clones with an established Th1 profile of cytokine secretion did express mRNA for, and produced detectable amounts of, IL-4 when stimulated with P in combination with insoluble anti-CD3 mAb. Combined stimulation with P and insoluble anti-CD3 mAb also enabled Th1 clones to express CD30 on their surface membrane. These results indicate that P can favor the development of Th cells producing Th2-type cytokines and is an inducer of both transient IL-4 production and CD30 expression in established Th1 cells. Thus, P production at the placental level may be responsible, at least in part, for increased production of Th2-type cytokines which have been implied in fetal allograft survival and maintenance of successful pregnancy.

Antigens, Surface↗
PubMed1995

Maternal serum CA 125 levels in first trimester abortion.

OBJECTIVE: To assess the source of maternal serum CA 125 during the first trimester of pregnancy. STUDY DESIGN: CA 125 was measured in stored samples from nonviable pregnancies of 8-13 weeks gestation. The study group comprised 19 women with vaginal bleeding and 13 non-bleeders. Only patients in whom chromosome analysis of the products of conception demonstrated a normal caryotype were included. CA 125 levels were expressed in multiples of the median (MoM) for normal pregnancies of the same gestational age. RESULTS: Median MoM values of CA 125 were significantly higher in women with vaginal bleeding (1.81 MoM) as compared both to non-bleeders (0.82 MoM; p < 0.01-Mann-Whitney U-test) and to the normal pregnancies (1.01 MoM; p < 0.05). No significant difference was found between non-bleeding women and controls. CONCLUSIONS: The present study indicates that in non-viable pregnancies with euploid fetuses an increase in maternal serum CA 125 levels was found only in presence of decidual disruption associated to vaginal bleeding. These findings are compatible with a prevalent decidual source of this antigen.

Abortion, Spontaneous↗
PubMed1995

I. Aging of the human endometrium: a basic morphological and immunohistochemical study.

OBJECTIVE: To evaluate if human endometrium presents morphological variations suggestive of an age-related decline in endometrial receptivity. STUDY DESIGN: Peri-implantation endometrium of younger (<30 years of age: n = 13) and older (>40 years of age: n = 17) normally menstruating women was studied. Endometrial specimens were routinely fixed in buffered formalin and embedded in paraffin. Sections (5 mu m) were stained with hematoxylin-eosin, periodic acid-Schiff (PAS) and Trichrome conforming to Masson according to conventional histologic examination. Several consecutive sections were used for the following immunohistochemical study: vascular localization (CD34), cellular proliferation index (PCNA), progesterone and estrogen receptors. RESULTS: Using both the traditional morphological evaluation and monoclonal antibodies, no significant differences were found between the endometria of women <30 years of age and those of women >40. CONCLUSIONS: Our results suggest that human endometrium does not age, at least while cyclic hormonal stimulation and menstruation are present.

Adult↗
PubMed1995

Activation of HIV expression by CD30 triggering in CD4+ T cells from HIV-infected individuals.

CD30 is a member of the tumor necrosis factor receptor superfamily, preferentially expressed by T cells producing type 2 helper (Th2) cytokines, whose ligand (CD30L) has been identified on B cells, activated macrophages, and a subset of activated T cells. We show here that cross-linking CD30 with an agonistic CD30-specific monoclonal antibody, as well as with CD30L+ CD8+ T cell clones or CD30L+ B cells, enhanced HIV replication in CD4+ T cells from HIV-infected individuals, and such a potentiating effect was inhibited by anti-CD30L antibody. The anti-CD30L antibody also exerted a suppressive effect on spontaneous HIV replication occurring in lymph node cells from an HIV-sero-positive patient, showing CD30L expression by both B and CD8+ T lymphocytes. Thus, CD30 triggering by CD30L-expressing cells may plan an important role in the activation of HIV expression from latently infected CD4+ T cells.

B-Lymphocytes↗
PubMed1995

Amniotic fluid levels of CA 19.9 and CA 15.3 in normal and Down's syndrome pregnancies.

CA 125, CA 19.9 and CA 15.3 are antigenic determinants on glycoproteins commonly used as serum markers in gynecologic oncology. CA 125 was also investigated in the amniotic compartment of Down's syndrome pregnancies. The objective of this study was to evaluate the concentration of CA 19.9 and CA 15.3 in the amniotic fluid of normal and Down pregnancies. The concentration of these antigens was measured in stored amniotic fluid samples from 15-19 weeks pregnancies with and without Down's syndrome fetuses and expressed in multiples of the median for normal pregnancies of the same gestational age. The study group included 20 samples selected from single Down's syndrome pregnancies. Each of these samples were matched with three control samples from unaffected pregnancies, matched for maternal age, gestational age and duration of storage of the sample. The median MoM values of CA 19.9 and CA 15.3 in Down's syndrome pregnancies were respectively 1.11 MoM and 1.16 MoM, not significantly different from those of unaffected pregnancies (CA 19.9: 1.02 MoM; CA 15.3: 0.99 MoM). In the present study we have not found significantly different levels of CA 19.9 and CA 15.3 in the amniotic fluid of fetuses affected by Down's syndrome and in the controls.

Amniotic Fluid↗
PubMed1994

CD30 expression by CD8+ T cells producing type 2 helper cytokines. Evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection.

A large panel of CD8+ T cell clones generated from peripheral blood lymphocytes (PBL) of healthy donors or human immunodeficiency virus (HIV)-infected individuals were assessed for both cytokine secretion profile and CD30 expression and release. The great majority of CD8+ T cell clones generated from healthy individuals showed the ability to produce interferon gamma (IFN-gamma), but not interleukin 4 (IL-4), and none of them either expressed membrane CD30 or released substantial amounts of soluble CD30 (sCD30) in their supernatant. In contrast, high numbers of CD8+ T cell clones generated from HIV-infected individuals, which produced IL-4 (and IL-5) in addition to IFN-gamma or IL-4 (and IL-5) alone, expressed membrane CD30 and released detectable amounts of sCD30 in their supernatants. Indeed, CD30 expression appeared to be positively correlated with the ability of CD8+ T cell clones to produce IL-4 and IL-5 and inversely correlated with their ability to produce IFN-gamma, whereas no correlation between CD30 expression and production of IL-10 was observed. These data suggest that CD30 is a marker for CD8+ T cells that have switched to the production of type 2 helper cytokines.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Th2-like CD8+ T cells showing B cell helper function and reduced cytolytic activity in human immunodeficiency virus type 1 infection.

We analyzed at clonal level the functional profile of circulating or skin-infiltrating T lymphocytes from two individuals infected with the human immunodeficiency virus type 1 (HIV-1), suffering from a Job's-like syndrome (eczematous dermatitis, recurrent skin and sinopulmonary infections, and hypergammaglobulinemia E) and showing virtually no circulating CD4+ T cells. Most of the CD3+ T cell clones generated from both patients were CD4- CD8+ TCR alpha beta +. The others were CD4- CD8- TCR alpha beta + which exhibited reduced mRNA expression for the CD8 molecule or no mRNA expression for either CD4 or CD8 molecules. The great majority of both CD4- CD8+ and CD4- CD8- did not produce interferon (IFN) gamma and exhibited reduced cytolytic activity. Rather, most of them produced large amounts of both interleukin (IL) 4 and IL-5 and provided B cell helper function for IgE synthesis. These data suggest that a switch of cytolytic CD8+ T cells showing a Th1-like cytokine secretion profile to cells that make Th2-type cytokines, exhibit reduced cytolytic potential, and provide B cell helper function can occur in the course of HIV-1 infection. These cells may contribute to the reduced defense against viral infections and intracellular parasites and account for the elevated IgE serum levels, eosinophilia, and the allergic-like clinical manifestations seen in a proportion of HIV-1-infected individuals.

B-Lymphocytes↗
PubMed1994

Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.

Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.

Animals↗
PubMed1994

Humerus and femur length in fetuses with Down syndrome.

The aim of the study was to assess the value of sonographic measurement of fetal humerus and femur lengths in the second trimester as a screening tool for Down syndrome (DS). We reviewed retrospectively fetal sonographic biometry made at the time of amniocentesis between 15 and 19 weeks. The study group consisted of 27 DS fetuses. The control group comprised 500 normal fetuses chosen randomly. The expected humeral and femoral lengths for a given biparietal diameter were estimated by linear regression equations from the 500 normal fetuses. Receiver operating characteristic curve analysis was performed to evaluate both the detection rate and the false-positive rate of different cut-off values of measured to expected lengths ratios. The median femur and humeral lengths in DS fetuses were 0.91 times the expected values. No significant differences in the detection rate and false-positive rate were found between the humerus and femur lengths. When the humeral and femoral lengths were combined, we observed a remarkable reduction in the false-positive rate. A measured to expected length ratio of 0.91 detected 44.4 per cent of DS fetuses with 7.6 per cent false positives. These results suggest that the combination of femoral and humeral lengths may permit a more efficient use of ultrasound in screening for Down syndrome than the use of either alone.

Down Syndrome↗
PubMed1994

Spontaneous in vitro differentiation of a myoepithelial cell line (PA 16/23) from a pleomorphic adenoma of the parotid gland is associated with reduced production of the autocrine growth factor interleukin 6.

A myoepithelial cell line (PA 16/23) was derived from a pleomorphic adenoma of the parotid gland. PA 16/23 cells have light microscopic, immunophenotypical and ultrastructural features of immature myoepithelial cells, i.e. they are of fusiform or stellate shape and show keratin and actin cytofilaments located mainly in the perinuclear cytoplasm, desmosomes and tracts of basal lamina. The PA 16/23 cells grew actively and expressed mRNA for and produced interleukin 6 (IL-6) which was released into the culture medium. This cytokine, in turn, acted as an autocrine growth factor on the cells. PA 16/23 cells also expressed high-affinity IL-6 receptors. In these cells, both IL-6 production and proliferation could be modulated by exogenous stimulants, such as IL-6 itself, IL-1, IL-4, tumour necrosis factor alpha, interferon gamma and lipopolysaccharide. From the 40th culture passage onwards, the PA 16/23 cells ceased to grow, either spontaneously or in response to exogenous stimulants. Moreover, they strongly reduced IL-6 production, and underwent morphological differentiation into more mature myoepithelial cells, with an increased amount and a different arrangement of the keratin and actin cytofilaments, which formed thick bundles in the peripheral cytoplasm. These findings suggest a role for IL-6 in modulating the proliferation and, possibly, the differentiation of the PA 16/23 cells.

Actins↗
PubMed1994

[The use of Rossavik's mathematical model in determining individual intrauterine growth curves. Our experience].

OBJECTIVE: To evaluate the performance of Rossavik growth models, derived from II trimester ultrasound measurements, to predict growth in normally growing fetuses. DESIGN: Comparison between observed measurements after 25 weeks and those predicted by Rossavik growth models determined from the data collected in 2 ultrasound examinations at approximately 16 weeks and 24 weeks. SETTING: Teaching hospital obstetric unit, in Florence. SUBJECTS: Thirty women who delivered normal term fetuses in our unit, between January 1991 and December 1992. MAIN OUTCOME MEASURES: Determination of the expected growth curve after 25 weeks from the appropriate growth models, for these fetal parameters: biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The differences between sonographic measurement of each parameter, at various time points, and predicted values were expressed as a percentage of the predicted values. Head circumference and weight measured in each infant were also compared with the predicted values at term. RESULTS: Mean percent deviation values were comprised between -0.02% (+/- 2 SD: 3.9%) for BPD and +0.75% (+/- 2 SD: 4.6%) for FL. Pearson's correlation coefficients between predicted and observed fetal parameters, ranged from 0.89 for AC and 0.94 for BPD. For HC and estimated weight at birth, the percent deviations were 0.84% (+/- 2 SD: 5.6%) and 1.23% (+/- 2 SD: 10.5%), respectively. The mean percent deviations for all parameters, were not significantly different from zero. CONCLUSIONS: Our results confirm the accuracy of Rossavik growth model in predicting growth after 25 weeks in normally growing fetuses.

Biometry↗
PubMed1993

Immortalization with herpesvirus saimiri modulates the cytokine secretion profile of established Th1 and Th2 human T cell clones.

T blasts of six established human CD4+ T cell clones with defined Ag specificity and cytokine secretion profile (3 Th1 and 3 Th2) were immortalized with Herpesvirus saimiri (HVS) and compared with their uninfected counterparts for their ability to proliferate, produce cytokines, and express cytolytic activity. HVS-transformed Th1 and Th2 clones neither substantially changed their original surface markers nor lose their ability to proliferate in response to their specific Ag but did acquire the ability to proliferate in response to contact signals delivered by SRBC or autologous APC alone. In addition, transformation by HVS substantially enhanced the lectin-dependent cytolytic activity of Th1 clones and enabled noncytolytic Th2 clones to exert cytolytic activity. HVS-transformed Th1 clones but not their uninfected counterparts spontaneously transcribed and secreted Th1-type cytokines (IL-2, IFN-gamma, and TNF-beta) and such a production was further enhanced by stimulation with either SRBC or PMA plus anti-CD3 mAb. HVS transformed but not uninfected Th2 clones constitutively expressed both IL-4 and IL-2 mRNA and secreted IFN-gamma. Stimulation with PMA plus anti-CD3 mAb induced uninfected Th2 clones to secrete high amounts of IL-4 and IL-5 but not Th1-type cytokines, whereas the same HVS-transformed Th2 showed minimal IL-4 and IL-5 secretion with concomitant high production of IL-2, IFN-gamma, and TNF-beta. Transformation by HVS also resulted in up-regulation of TNF-alpha and IL-3 production by both Th1 and Th2 clones. The ongoing proliferation of HVS-transformed clones was partially inhibited by either anti-IL-2 or anti-IL-3 antibodies and virtually abolished by the combined addition of the two anticytokine antibodies, suggesting that both IL-2 and IL-3 can function as autocrine growth factors for HVS-transformed Th1 and Th2 clones.

Cell Transformation, Viral↗
PubMed1993

Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production.

IL-10 gene transcription and IL-10 protein production was assessed in both type 1 (Th1) and type 2 (Th2) CD4+ human T cell clones by polymerase chain reaction and ELISA, respectively. Although Th2 clones apparently showed higher IL-10 mRNA levels, IL-10 mRNA expression was consistently found in Th1 clones, as well. Likewise, measurable IL-10 levels were found in the supernatants of both Th1 and Th2 clones. The effect of human IL-10 (h-IL-10) and viral IL-10 (v-IL-10) on the proliferative response and cytokine production by Th1 and Th2 human clones was also investigated. Addition in culture of h-IL-10 and v-IL-10 significantly reduced the proliferation of both Th1 and Th2 clones in response to the specific Ag and to PHA, but it had no inhibitory effect on the proliferative response of Th1 and Th2 clones to IL-2. h-IL-10 and v-IL-10 also inhibited the Ag-induced production of gamma-interferon (IFN-gamma) by Th1 clones and the production of IL-4 and IL-5 by Th2 clones, whereas they had no effect on the cytokine synthesis by the same clones stimulated with PMA plus anti-CD3 antibody. Preincubation of APC, but not of clonal T blasts, with h-IL-10 resulted in the inhibition of Ag-induced proliferation of both Th1 and Th2 clones, supporting the view that h-IL-10 primarily affects APC. These data demonstrate that, unlike the murine system where IL-10 is a product of Th2 (but not Th1) cells and seems to mainly down-regulate the Th1 response, in the human system, IL-10 is produced by, and down-regulates the function of, both Th1 and Th2 cells.

Animals↗
PubMed1993

Abnormal amniotic fluid levels of CA 125 in second-trimester Down syndrome pregnancies.

The aim of this study was to evaluate the concentration of CA 125 in second trimester amniotic fluid from Down syndrome pregnancies. CA 125 was measured in stored amniotic fluid samples from pregnancies of 14-19 weeks' gestation with and without Down syndrome fetuses. CA 125 levels were expressed in multiples of the median (MOM) for normal pregnancies of the same gestational age. Twenty-one pregnancies with Down syndrome fetuses and 63 unaffected controls matched for maternal age, gestational age, and duration of storage were studied. The median MOM values of the affected pregnancies were significantly higher than those of the controls (1.41 MOM versus 0.99 MOM). These findings show that there is an increased concentration of CA 125 in second-trimester amniotic fluid from Down syndrome pregnancies.

Amniotic Fluid↗
PubMed1992

[Echographic measuring of the length of the fetal femur in the screening for Down syndrome].

OBJECTIVE: Our purpose was to assess the value of sonographic measurement of fetal femur length in the second trimester, as a screening tool for Down's syndrome. STUDY DESIGN: We evaluated a consecutive series of fetuses scanned by a single sonologist at the time of amniocentesis between 15 and 19 weeks. The study group consisted of fetuses with Down's syndrome (N = 16); the control group comprised normal fetuses (N = 1163). A linear regression model of the normal femur length based on biparietal diameter (BPD), was established for our population; the ratios of measured to expected femur length for a viven BPD (FL M/E) were calculated in the two groups. To test statistical significance of observed differences between case and control population, unpaired t test was used. The ability of specific FL M/E cut-off values to discriminate between Down syndrome and normal fetuses was assessed by Fisher's exact test. RESULTS: The mean ratio of measured to expected femur length was significantly lower in the Down syndrome as compared with control population (0.9473, DS 0.0795) versus 1.0, DS 0.0745) (p < 0.0045). The ratio of 0.91 or less predicted Down's syndrome with a sensitivity of 43.7% and a false-positive rate of 8.6%. For women with risk of one in 250 and one in 1000 of having an affected fetus based on maternal age, a shortened femur yielded positive predictive values of one in 26 and one in 105, respectively. CONCLUSION: These results suggest that the sonographic measurement of fetal femur length for the screening of Down syndrome in the low-risk population is hindered by a high false positive rate (about 9%). It follows that the percentage of women requiring an amniocentesis would increase to un unacceptably high level. The utilization of this biometric marker may be helpful, in our opinion, for identifying fetuses at risk for Down syndrome in women between 35 and 38 years of age. These women in fact, are not offered amniocentesis for the prenatal diagnosis of Down's syndrome in the majority of italian institutions. The sonographic measurement of fetal femur length could detect about 45% of fetal Down's syndrome, offering an amniocentesis to 9% of women, with a consequent reduction of the cost required. Only a prospective study can evaluate the efficacy of this method to predict Down syndrome in such group of women.

Adult↗
PubMed1991

Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production.

A large series of T cell clones (TCC) specific for purified protein derivative (PPD) of Mycobacterium tuberculosis (total 60) or Toxocara canis excretory/secretory (TES) antigen (total 69) were established from the peripheral blood of two healthy individuals and analyzed for their profile of cytokine production in response to stimulation with either the specific antigen or the polyclonal activator phorbol myristate acetate plus anti-CD3 antibody. Under both these experimental conditions, the great majority of PPD-specific TCC secreted IL-2 and IFN-gamma but not, or limited amounts of, IL-4 and IL-5. In contrast, most TES-specific TCC secreted IL-4 and IL-5 but not, or limited amounts of, IL-2 and IFN-gamma. PPD-specific TCC that failed to secrete IL-4 and IL-5, and TES-specific TCC that failed to secrete IL-2 and IFN-gamma, were found to lack transcripts for IL-4 and IL-5, or for IL-2 and IFN-gamma, respectively. During the course of the study, over a 6-mo period, the functional phenotype of both TES- and PPD-specific TCC was repeatedly assessed and remained constant. These data demonstrate that T cells with stable Th1 or Th2 functional pattern exist not only in mice but also in humans and suggest that in the course of natural immunization certain infectious agents preferentially expand T cell subsets with stable and definite profile of cytokine production.

Adult↗