Search PubMed⌕ Search

Biomedical subjects

E Maggi

Publications and source records attributed to E Maggi.

At least 19 recordsLinked to original sources
PubMed2001

Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) alphabeta+ CD8+ single-positive T cells, TCRgammadelta+ T cells, and natural killer-type cells in human thymus.

Strong reactivity for interferon-inducible protein 10 (IP-10), monokine induced by interferon gamma (Mig), and interferon-inducible T-cell alpha chemoattractant (I-TAC) was found in epithelial cells mainly localized to the medulla of postnatal human thymus. The CXC chemokine receptor common to the 3 chemokines (CXCR3) was also preferentially expressed in medullary areas of the same thymuses and appeared to be a property of 4 distinct populations: CD3+ T-cell receptor (TCR) alphabeta+ CD8+ single-positive (SP) T cells, TCRgammadelta+ T cells, natural killer (NK)-type cells, and a small subset of CD3+(low) CD4+ CD8+ TCRalphabeta+ double-positive (DP) T cells. IP-10, Mig, and I-TAC showed chemoattractant activity for TCRalphabeta+ CD8+ SP T cells, TCRgammadelta+ T cells, and NK-type cells, suggesting their role in the migration of different subsets of mature thymocytes during human thymus lymphopoiesis.

CD8-Positive T-Lymphocytes↗
PubMed2001

Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity.

Endothelial cell receptors for the angiostatic chemokines IFN-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by IFN-gamma (Mig) have not yet been identified, and the mechanisms responsible for the effects of these chemokines on angiogenesis are still unclear. IP-10 and Mig share a common functional receptor on activated T lymphocytes, named CXC chemokine receptor 3 (CXCR3). Using in situ hybridization and immunohistochemistry, we show that CXCR3 is expressed by a small percentage of microvascular endothelial cells in several human normal and pathological tissues. Primary cultures of human microvascular endothelial cells (HMVECs) likewise express CXCR3, although this expression is limited to the S/G2-M phase of their cell cycle. Both IP-10 and Mig, as well as the IFN-gamma-inducible T-cell alpha chemoattractant (I-TAC), which all share high-affinity binding for CXCR3, block HMVEC proliferation in vitro, an effect that can be inhibited by an anti-CXCR3 antibody. These data provide definitive evidence of CXCR3 expression by HMVEC and open new avenues for therapeutic interventions in all conditions in which an angiostatic effect may be beneficial.

Angiogenesis Inhibitors↗
PubMed2000

Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy.

Development of CD4+ helper T (Th) cells into type 1 (Th1) or type 2 (Th2) effectors, as characterized by their opposite pattern of cytokine production, can be influenced by several factors, including hormones. Progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-gamma by T cells. Leukemia inhibitory factor (LIF), essential for embryo implantation, is up-regulated by IL-4 and progesterone. Moreover, the production of LIF and/or Th2 cytokines by decidual T cells contributes to the maintenance of pregnancy. Our results suggest that relaxin and progesterone may contribute to the regulation of the immune homeostasis during pregnancy.

Cytokines↗
PubMed2000

Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: possible implications for negative selection.

The chemoattractant activity of macrophage-derived chemokine (MDC), EBI1-ligand chemokine (ELC), and secondary lymphoid tissue chemokine (SLC) on human thymocytes was analyzed. Both ELC and SLC caused the accumulation of CD4+CD8- or CD4-CD8+ CD45RA+ thymocytes showing high CD3 expression. By contrast, a remarkable proportion of MDC-responsive thymocytes were CD4+CD8+ cells exhibiting reduced levels of CD8 or CD4+CD8- cells showing CD3 and CD45R0, but not CD45RA. MDC-responsive thymocyte suspensions were enriched in cells expressing the MDC receptor, CCR4, selectively localized to the medulla, and in CD30+ cells, whereas ELC-responsive thymocytes never expressed CD30. Reactivity to both MDC and ELC was localized to cells of the medullary areas, but never in the cortex. Double immunostaining showed no reactivity for either MDC or ELC by T cells, macrophages, or mature dendritic cells, whereas many medullary epithelial cells were reactive to MDC or ELC. However, MDC reactivity was consistently localized to the outer wall of Hassal's corpuscles, whereas ELC reactivity was often found in cells surrounding medullary vessels, but not in Hassal's corpuscles. Moreover, while most MDC-producing cells also stained positive for CD30L, this molecule was never found on ELC-producing cells. We suggest therefore that CD30L-expressing MDC-producing medullary epithelial cells attract CCR4-expressing thymocytes, thus favoring the CD30/CD30L interaction, and therefore the apoptosis, of cells that are induced to express CD30 by autoantigen activation. By contrast, ELC production by CD30L-lacking medullary epithelial cells may induce the migration into periphery of mature thymocytes that have survived the process of negative selection.

Cell Differentiation↗
PubMed2000

Limited expression of R5-tropic HIV-1 in CCR5-positive type 1-polarized T cells explained by their ability to produce RANTES, MIP-1alpha, and MIP-1beta.

Human T helper (Th) cells (Th1- or Th2-oriented memory T cells as well as Th1- or Th2-polarized naive T cells) were infected in vitro with an R5-tropic HIV-1 strain (BaL) and assessed for their profile of cytokine production, CCR5 receptor expression, and HIV-1 p24 antigen (p24 Ag) production. Higher p24 Ag production was found in CCR5-negative Th2-like memory T cells than in CCR5-positive Th1-like memory T cells. By contrast, p24 Ag production was higher in Th1-polarized activated naive T cells in the first 4 days after infection. However, p24 Ag production in Th1-polarized T cells became comparable or even lower than the production in Th2-polarized populations later in infection or when the cells were infected with HIV-1BaL after secondary stimulation. The higher levels of p24 Ag production by Th1-polarized naive T cells soon after infection reflected a higher virus entry, as assessed by the single round infection assay using the HIV-chloramphenicol acetyl transferase (HIV-CAT) R5-tropic virus that contains the envelope protein of HIV-1 YU2 strain. The limitation of viral spread in the Th1-polarized populations, despite the initial higher level of T-cell entry of R5-tropic strains, was due to the ability of Th1 cells to produce greater amounts of beta-chemokines than Th2 cells. In fact, an inverse correlation was observed between Th1-polarized naive T cells and Th1-like memory-activated T cells in regards to p24 Ag production and the release of the following CCR5-binding chemokines: regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Moreover, infection with the HIV-1BaL strain of Th1-polarized T cells in the presence of a mixture of anti-RANTES, anti-MIP-1alpha, and anti-MIP-1beta neutralizing antibodies resulted in a significant increase of HIV-1 expression. These findings suggest that Th1-type responses may favor CD4(+) T-cell infection by R5-tropic HIV-1 strains, but HIV-1 spread in Th1 cells is limited by their ability to produce CCR5-binding chemokines. (Blood. 2000;95:1167-1174)

Adult↗
PubMed2000

Macrophage-derived chemokine production by activated human T cells in vitro and in vivo: preferential association with the production of type 2 cytokines.

Macrophage-derived chemokine (MDC), a potent chemoattractant for chronically activated Th2 lymphocytes, is constitutively expressed by dendritic cells, B cells, macrophages, and thymic medullary epithelial cells, whereas monocytes, NK cells, and T lymphocytes produce MDC only upon appropriate stimulation. In this study, we show in vitro MDC production also by activated T cells, which preferentially associate with the production of Th2 cytokines, IL-4, IL-5, and IL-6, and inversely correlate with the production of the Th1 cytokine, IFN-gamma. Moreover, high levels of MDC were detected in the sera of the great majority of subjects suffering from mycosis fungoides/Sézary syndrome or atopic dermatitis, which are considered as disorders characterized by the predominant expansion and activation of Th2 cells, respectively. By contrast, serum MDC levels in subjects with multiple sclerosis or Crohn's disease, which are characterized by a Th1 predominance, did not differ significantly from those of healthy controls. Finally, MDC expression was detected in the skin biopsy specimens of subjects with atopic dermatitis, where it was expressed by both dendritic cells and T lymphocytes. Taken together, these findings suggest that MDC production by activated T cells may occur both in vitro and in vivo, particularly in association with Th2 cytokines, thus providing an important amplification circuit for Th2-mediated responses.

Biopsy↗
PubMed2000

Role of hormone-controlled T-cell cytokines in the maintenance of pregnancy.

Human CD4 T helper lymphocytes can be subdivided into at least three distinct functional subsets on the basis of their cytokine secretion profiles. One type of CD4+ lymphocyte, T helper 1 (Th1), produces interferon (IFN)-gamma and tumour necrosis factor beta, a second type (Th2) produces interleukin (IL)-4 and IL-5 and a third type (Th0) produces both Th1 and Th2 cytokines. The apparent paradox that embryos are not rejected by the maternal immune system despite the presence of paternal MHC histocompatibility antigens has been explained in mice by a Th2 switch at the level of the materno-fetal interface. We showed that some hormones enhanced during pregnancy can affect the development of Th1 and Th2 responses. Indeed, we found that progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-gamma by T-cells. In addition, we showed that leukaemia inhibitory factor (LIF), which is essential for embryo implantation, associates with Th2 cells and is upregulated by IL-4 and progesterone. We also showed that LIF is down-regulated by Th1 inducers [IL-12, IFN-gamma and IFN-alpha]. Furthermore, we found a decreased production of LIF, IL-4 and IL-10 by decidual T-cells in women with unexplained recurrent abortions in comparison with women with normal gestation at the moment of voluntary abortion. The decreased production of LIF, IL-4 and IL-10 was not found in peripheral-blood T-cells. These results suggest that the local production of LIF and/or Th2 cytokines may contribute to the maintenance of pregnancy.

Abortion, Spontaneous↗
PubMed2000

Enhanced expression of the CXCR4 co-receptor in HIV-1-infected individuals correlates with the emergence of syncytia-inducing strains.

The aim of this study was to investigate the mechanisms responsible for the emergence in some HIV-1-infected individuals of highly aggressive, syncytia-inducing (SI) HIV-1 strains, which have been shown to use CXCR4 as co-receptor to enter target cells. To this end, the percentages of circulating CXCR4+CD4+ T cells were evaluated by flow cytometry in 39 untreated and 61 highly active antiretroviral therapy (HAART)-treated HIV-1-infected individuals in comparison with 35 HIV-1 seronegative subjects. Plasma viremia was also measured, and HIV primary isolates, from both untreated and HAART-treated HIV-1-infected subjects, were tested for the presence of SI strains. The results of this study showed enhanced proportions of CXCR4+CD4+ T cells in untreated patients in comparison with HAART-treated and healthy subjects. Furthermore, the results of a 12-month longitudinal study in a cohort of 11 patients undergoing HAART showed a significant reduction of CXCR4 expression after successful therapy. Finally, a significant positive correlation among the proportions of circulating CXCR4-expressing CD4+ T cells, plasma viremia, and the probability to isolate SI strains was found. These in vivo data are in keeping with previous in vitro results suggesting a bidirectional link between HIV-1 and CXCR4 expression on CD4+ T cells, and provide some clues to understanding the mechanisms exerting a selective pressure toward the emergence of SI strains.

Adult↗
PubMed2000

Environmental factors favoring the allergen-specific Th2 response in allergic subjects.

Allergen-reactive type 2 helper T cells (Th2) play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells, and eosinophils, i.e., the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a positive role. In contrast, cytokines such as interferon (IFN)-alpha, IFN-gamma, IL-12, and transforming growth factor (TGF)-beta, and relaxin play a negative regulatory role on the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic individuals still remain obscure. Some gene products selectively expressed in Th2 cells or selectively controlling the expression of IL-4 have recently been described. Moreover, cytokines and other gene products that dampen the production of IL-4, as well as the development and/or the function of Th2 cells, have been identified. These findings allow us to suggest that the upregulation of genes controlling IL-4 expression and/or abnormalities of regulatory mechanisms of Th2 development and/or function may be responsible for Th2 responses against common environmental allergens in atopic subjects.

Allergens↗
PubMed2000

Genetic and environmental factors contributing to the onset of allergic disorders.

Evidence has been accumulated to suggest that allergen-reactive Th2 cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in allergic inflammation. Recently, chemokines and chemokine receptors involved in such Th2-type response have been also defined. Th2 cells represent the polarized arm of the effector-specific responses that contribute to the protection against gastrointestinal nematodes and act as regulatory cells for chronic and/or excessive Th1-mediated responses. Th2 cells are generated from precursor naive Th cells when they encounter the specific antigen in an IL-4-containing microenvironment. The question of how these Th2 cells are selected in atopic patients is also unclear. Both the nature of the T cell receptor signalling provided by the allergen peptide ligand and a disregulation of IL-4 production likely concur to determine the Th2 profile of allergen-specific Th cells, but the genetic unbalanced IL-4 production is certainly overwhelming. Some gene products selectively expressed in Th2 cells or selectively controlling the expression of IL-4 have recently been described. These findings allow to suggest that the upregulation of genes controlling IL-4 expression and/or abnormalities of regulatory mechanisms of Th2 development and/or function may be responsible for Th2 responses against allergens in atopic people. The increasing prevalence of allergy in developed countries suggests that environmental factors acting either before or after birth also contribute to regulate the development of Th2 cells and/or their function. The reduction of infectious diseases in early life due to increasing vaccinations, antimicrobial treatments as well as changed lifestyle are certainly important in influencing the individual outcome in the Th response to ubiquitous allergens. Moreover, the recent evidence that bacterial DNA or oligodeoxynucleotides containing unmethylated 'CpG motifs' promote the development of Th1 cells via the production of immunomodulatory cytokines (namely IL-12, IL-18 and IFNs) by professional antigen-presenting cells confirms previous epidemiological data. The new insight into the pathophysiology of T cell responses in atopic diseases provides exciting opportunities for the development of novel immunotherapeutic strategies.

Adjuvants, Immunologic↗
PubMed2000

Comparison of Vero cell assay, polymerase chain reaction and an enzyme immunoassay for identification of verocytotoxin-producing Escherichia coli O157:H7.

This study evaluated three different analytical methods for identification of Verocytotoxin-producing E. coli O157:H7 (VTEC) strains. A total of 34 E. coli O157:H7 strains isolated from bovine faeces and bovine carcasses were comparatively tested with Vero cell assay (VCA), PCR and the sandwich ELISA "RIDASCREEN Verotoxin" test. The VCA, performed without a neutralization assay, gave a false positive result because a VCA-positive E. coli O157:H7 strain did not possess the VT-coding genes when tested with PCR. The lack of specificity of the VCA could be avoided by testing for neutralization of cytotoxicity. The commercial ELISA system was as sensitive and specific as PCR, with the advantages of being a more rapid and easier procedure which could be employed in all first level diagnostic laboratories.

Abattoirs↗
PubMed2000

Th1/Th2 cells, their associated molecules and role in pathophysiology.

Cytokines, chemokines, and/or chemokine receptors associated with type 1 T helper (Th1) or Th2 cells play a role in different physiological conditions, such as T lymphopoiesis and pregnancy, as well as in pathological conditions, such as unexplained recurrent abortions, proliferative glomerulonephritis, and control of angiogenesis.

Abortion, Habitual↗
PubMed1999

Phosphorothioate oligodeoxynucleotides promote the in vitro development of human allergen-specific CD4+ T cells into Th1 effectors.

DNA vaccination is an effective approach in inducing the switch of murine immune responses from a Th2 to a Th1 profile of cytokine production that has been related to the activity of unmethylated CpG motifs present in bacterial, but not mammalian, DNA. We report here that some synthetic phosphorothioate, but not phosphodiester, oligodeoxynucleotides (ODNs) were able to induce B cell proliferation and to shift the in vitro differentiation of Dermatophagoides pteronyssinus group 1-specific human CD4+ T cells from atopic donors into Th cell effectors showing a prevalent Th1, instead of Th2, cytokine profile. This latter effect was completely blocked by the neutralization of IL-12 and IFN (alpha and gamma) in bulk culture, suggesting that the Th1-inducing activity of phosphorothioate ODNs was mediated by their ability to stimulate the production of these cytokines by monocytes, dendritic, and NK cells. Cytosine methylation abolished the Th1-inducing activity of ODNs; however, CpG dinucleotide-containing ODNs exhibited the Th1-shifting effect independently of the presence or the absence of CpG motifs (5'-pur-pur-CpG-pyr-pyr-3'). Moreover, the inversion of CpG to GpC resulted only in a partial reduction of this activity, suggesting that the motif responsible for the Th1-skewing effect in humans is at least partially different from that previously defined in mice. These results support the concept that the injection of allergens mixed to, or conjugated with, appropriate ODNs may provide a novel allergen-specific immunotherapeutic regimen for the treatment of allergic disorders.

Adult↗
PubMed1999

CD30-CD30 ligand interaction in primary cutaneous CD30(+) T-cell lymphomas: A clue to the pathophysiology of clinical regression.

Primary CD30(+) cutaneous T-cell lymphomas (CTCLs) represent a spectrum of non-Hodgkin's lymphomas (NHLs) that have been well defined at the clinical, histologic, and immunologic level. This group, which includes 2 main entities (large cell lymphoma and lymphomatoid papulosis [LyP]) and borderline cases, is characterized by the expression of CD30 antigen by neoplastic large cells at presentation, possible spontaneous regression of the skin lesions, and generally favorable clinical course. Although the functional relevance of CD30 and its natural ligand (CD30L) expression in most cases of NHL is presently undefined, previous studies indicate that CD30L is likely to mediate reduction of proliferation in CD30(+) anaplastic large-cell NHL. No information is currently available concerning the expression of CD30L in primary CD30(+) CTCLs. In this study, we investigated the immunophenotypic and genotypic expression of CD30 and CD30L in different developmental phases of skin lesions (growing v spontaneously regressing). By immunohistochemistry, CD30L expression was detected in regressing lesions only; by molecular analysis, the expression of CD30L was clearly higher in regressing lesions than in growing ones. CD30L, while expressed by some small lymphocytes, was most often coexpressed by CD30(+) neoplastic large cells, as demonstrated by 2-color immunofluorescence and by immunohistochemistry on paraffin sections. Taken together, these data suggest that CD30-CD30L interaction may play a role in the pathobiology of primary cutaneous CD30(+) lymphoproliferative disorders. In particular, CD30L (over)expression might have a major role in the mechanism of self-regression of skin lesions, the most distinctive clinical feature of this cutaneous lymphoma subtype.

Adult↗
PubMed1999

Highly Th2-skewed cytokine profile of beta-lactam-specific T cells from nonatopic subjects with adverse drug reactions.

A positive lymphocyte transformation test to beta-lactams (beta-L) was found in 12 of 29 subjects with adverse drug reaction (ADR) to beta-L, irrespective of either the type of clinical manifestation or the presence of specific serum IgE. Short-term T cell lines specific for penicillin G, amoxicillin, and ampicillin could be generated only from subjects with ADR (eight with positive and one with negative lymphocyte transformation test), while streptokinase and Dermatophagoides pteronyssinus group 1 (Der p 1)-specific T cells were obtained from all these subjects, from 7 atopic Der p-sensitive donors without history of ADR and 17 healthy nonatopic donors. Streptokinase-specific T cells from all subjects showed intracellular expression of IFN-gamma with poor or no IL-4, whereas Der p 1-specific T cells exhibited IFN-gamma but low or no IL-4 expression in nonatopics, and remarkable IL-4 expression in atopic donors. By contrast, all penicillin G-, ampicillin-, and amoxicillin-specific short-term T cell lines showed high intracellular expression of IL-4, IL-5, and IL-13, but poor or no expression of IFN-gamma, thus exhibiting a clear-cut Th2 profile. Accordingly, most penicillin G-specific T cell clones derived from two subjects with ADR released high concentrations of IL-4 alone or IL-4 and IFN-gamma. These data suggest that cytokines produced by Th2 cells play an important role in all beta-L-induced ADR, even when late clinical manifestations occur and an IgE-mediated mechanism is apparently indemonstrable.

Allergens↗
PubMed1999

Isolation of Verocytotoxin-producing Escherichia coli O157:H7 from cattle at slaughter in Italy.

Cattle arriving for slaughter at a large abattoir in northern Italy between April 1997 and January 1998 were examined for intestinal carriage of Verocytotoxin-producing Escherichia coli (VTEC) O157 using an immunomagnetic separation technique. Sixty sorbitol non-fermenting VTEC O157 strains were isolated from 59 (13.1%) of the 450 cattle examined. In particular, VTEC O157 was found in 37 (16.6%) of 223 feedlot cattle and in 22 (16.1%) of 137 dairy cull cows, but not in the 90 veal calves sampled. The isolation rate was higher during warm weather (17.5%), falling to an average of 2.9% during the winter months. VT-negative, O157 latex-agglutinating E. coli strains were isolated from 23 (5.1%) of the 450 animals. PCR analysis showed that all 60 VTEC O157 strains carried the VT2 gene and that 25 strains also carried the VT1 gene. In addition, four of the VT-negative, O157 latex-agglutinating E. coli strains carried the VT2 gene. Atypical biochemical features were observed in some VTEC O157: two strains (3.3%) showed beta-glucuronidase activity, and seven (11.7%) produced urease.

Abattoirs↗
PubMed1999

Relaxin favors the development of activated human T cells into Th1-like effectors.

Differentiation of naive CD4+ helper T (Th) cells into Th1 or Th2 effectors, as characterized by their opposite pattern of cytokine production, can be influenced by several factors, including hormones. In this study, we demonstrate that porcine relaxin, at concentrations ranging from 10(-10) to 10(-6) M, favors the in vitro development of human antigen-specific T cells into Th1-like effectors and enhances both IFN-gamma mRNA expression and IFN-gamma production by established human T cell clones. The promoting effect of relaxin on the development of IFN-gamma-producing cells was not due to a relaxin-induced release of IL-12 and/or IFN-alpha by antigen-presenting cells. These results suggest that relaxin may contribute to the regulation of the immune homeostasis during pregnancy and may also play some role in counteracting Th2-dominated disorders.

Animals↗