Biomedical subjects

Enrico Maggi

Publications and source records attributed to Enrico Maggi.

25 records · Page 2Linked to original sources

PubMed2002

Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes.

Phenotypic markers, localization, functional activities, and mechanisms of action in vitro of CD4(+)CD25(+) T cells, purified from postnatal human thymuses, were investigated. These cells showed poor or no proliferation in mixed lymphocyte culture (MLC), and suppressed in a dose-dependent fashion the proliferative response to allogeneic stimulation of CD4(+)CD25(-) thymocytes. Virtually all CD4(+)CD25(+) thymocytes constitutively expressed cytoplasmic T lymphocyte antigen (CTLA)-4, surface tumor necrosis factor type 2 receptor (TNFR2), and CCR8. They prevalently localized to perivascular areas of fibrous septa and responded to the chemoattractant activity of CCL1/I-309, which was found to be produced by either thymic medullary macrophages or fibrous septa epithelial cells. After polyclonal activation, CD4(+)CD25(+) thymocytes did not produce the cytokines interleukin (IL)-2, IL-4, IL-5, IL-13, interferon gamma, and only a very few produced IL-10, but all they expressed on their surface CTLA-4 and the majority of them also transforming growth factor (TGF)-beta1. The suppressive activity of these cells was contact dependent and associated with the lack of IL-2 receptor (IL-2R) alpha-chain (CD25) expression in target cells. Such a suppressive activity was partially inhibited by either anti-CTLA-4 or anti-TGF-beta1, and was completely blocked by a mixture of these monoclonal antibodies, which were also able to restore in target T cells the expression of IL-2R alpha-chain and, therefore, their responsiveness to IL-2. These data demonstrate that CD4(+)CD25(+) human thymocytes represent a population of regulatory cells that migrate in response to the chemokine CCL1/I-309 and exert their suppressive function via the inhibition of IL-2R alpha-chain in target T cells, induced by the combined activity of CTLA-4 and membrane TGF-beta1.

Abatacept↗

PubMed2002

Type 1 T helper cells specific for Candida albicans antigens in peripheral blood and vaginal mucosa of women with recurrent vaginal candidiasis.

The cytokine profile of circulating and vaginal T cells specific for immunodominant mannoprotein antigens of Candida albicans was analyzed in patients with recurrent vaginal candidiasis (RVC). Peripheral blood mononuclear cells (PBMC) from patients with RVC proliferated more than those from healthy subjects and expressed higher type 1:type 2 T helper cell cytokine ratios in response to C. albicans stimulation. A higher number of C. albicans-specific T cells was generated in PBMC from patients with RVC than in PBMC from healthy donors. C. albicans-specific T cell clones from patients with RVC produced higher levels of interferon (IFN)-gamma and lower levels of interleukin (IL)-4 than clones from control women. More important, a higher proportion of C. albicans-specific T cell clones was generated from lesional mucosa of patients with RVC than from normal mucosa, all of which produced IFN-gamma but not IL-4. These findings provide direct evidence that RVC is characterized by a highly polarized local and circulating type 1 T helper cell-like response against C. albicans antigens.

Adult↗

PubMed2002

Role of low nuclear grading of renal carcinoma cells in the functional profile of tumor-infiltrating T cells.

Tumor-infiltrating lymphocytes (TILs) from biopsies of 9 selected patients with pT1pN0M0 renal cell carcinoma (RCC) were analyzed at the clonal level for phenotypic distribution, cytokine secretion profile and antitumor cell proliferation and cytotoxicity. T-cell clones generated from RCCs were able to produce higher amounts of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) than the corresponding clones derived from peripheral blood mononuclear cells, thus suggesting a recruitment into tumors of T cells with peculiar functions. Moreover, CD4+ T-cell clones generated from TILs of nuclear grading 2 (G2)-type RCC patients produced significantly higher amounts of IL-4 and IL-10 and lower amounts of IFN-gamma than the corresponding clones generated from G1-type RCC and 2 renal angiomyolipoma (AML) patients. In addition, T-cell clones generated from lymphocytes infiltrating the peritumoral areas of G2-type, but not those from G1-type, RCC patients produced higher and lower amounts of IL-4 and IFN-gamma, respectively, than the corresponding clones derived from intratumoral T cells of the same patients. The proportion of T-cell clones derived from G2-type tumors and proliferating to autologous tumor cells (ATCs) was significantly lower than that of clones generated from G1-type RCC or AML patients. However, irrespective of their source, they exhibited similar cytokine profiles and produced comparable amounts of IL-4, IL-10 and IFN-gamma. Furthermore, the proportion and the production of both IL-4 and IFN-gamma of G2-type RCC-derived T-cell clones with cytotoxic activity against ATC were significantly lower than those of cytolytic clones generated from AML and G1-type RCCs. The concentrations of IL-4, IL-10 and IFN-gamma produced by the cytolytic clones from G2-type RCC were also lower than those produced by their noncytolytic counterparts obtained from the same patients. These data address the association of the nuclear grading of neoplastic cells with different local tumor-specific T-cell responses in RCC.

CD4-Positive T-Lymphocytes↗

PubMed2002

Th2-oriented profile of male offspring T cells present in women with systemic sclerosis and reactive with maternal major histocompatibility complex antigens.

OBJECTIVE: To characterize the cytokine production profile of male-offspring T cells reactive against maternal major histocompatibility complex (MHC) antigens present in the peripheral blood and/or skin from women with systemic sclerosis (SSc). METHODS: T cell clones were generated from peripheral blood and/or skin biopsy specimens from 3 women with SSc of recent onset and from peripheral blood from 3 healthy women, all of whom had 1 male child. All clones were screened for their proliferative response in vitro to maternal MHC antigens by measuring (3)H-thymidine uptake and for their expression of Y chromosome by using fluorescence in situ hybridization. The concentrations of interferon-gamma and interleukin-4 (IL-4) released by T cell clones in response to maternal MHC antigens were evaluated in culture supernatants, using appropriate enzyme-linked immunosorbent assays. RESULTS: Thirty-nine of 202 T cell clones generated from women with SSc and 11 of 312 from healthy women proliferated in vitro in response to maternal MHC antigens. Seven MHC-reactive T cell clones obtained from women with SSc and 1 obtained from healthy women exhibited the Y chromosome, thus indicating that the clones were derived from T cells of male offspring. All clones generated from male-offspring T cells of SSc women (but not from those of healthy women) produced significantly higher levels of IL-4 in response to stimulation with maternal MHC antigens than did all other clones generated from the same women. The other clones proliferated in response to maternal or allogeneic MHC antigens but did not exhibit the Y chromosome. CONCLUSION: Male-offspring T cells that are present in the blood and skin of women with SSc and react with maternal MHC antigens exhibit a Th2-oriented profile, supporting the possibility that a chronic graft-versus-host reaction attributable to long-term microchimerism plays a pathogenic role in SSc.

Adult↗

PubMed2002

IP-10 and Mig production by glomerular cells in human proliferative glomerulonephritis and regulation by nitric oxide.

High levels of expression of mRNA and protein for the chemokines interferon-gamma (IFN-gamma)-inducible protein of 10 kD (IP-10) (CXCL10) and the monokine induced by IFN-gamma (Mig) (CXCL9) were observed, by using in situ hybridization and immunohistochemical analyses, in kidney biopsy specimens from patients with glomerulonephritis (GN), particularly those with membranoproliferative or crescentic GN, but not in normal kidneys. Double-immunostaining or combined in situ hybridization and immunohistochemical analyses for IP-10, Mig, and proliferating cell nuclear antigen (PCNA) or alpha-smooth muscle actin (alpha-SMA) revealed that IP-10 and Mig production by resident glomerular cells was a selective property of glomeruli in which mesangial cells demonstrated active proliferation. IP-10 and Mig mRNA and protein were also expressed by primary cultures of human mesangial cells and human visceral epithelial cells after stimulation with IFN- gamma or with IFN-gamma plus tumor necrosis factor-alpha (TNF-alpha) (which produced greater stimulation). The induction of IP-10 and Mig mRNA and protein expression by IFN-gamma plus TNF-alpha was strongly inhibited by nitric oxide (NO) donors, such as sodium nitroprusside or S-nitroso-N-acetylpenicillamine, but not by cGMP analogues. Electrophoretic mobility shift assays demonstrated that NO donors repressed IP-10 gene transcription induced by IFN-gamma plus TNF-alpha through the inhibition of NF-kappaB activation. These data demonstrate that resident glomerular cells in kidneys of patients with proliferative GN produce large amounts of IP-10 and Mig, which may play important pathogenic roles in this disease. These data also indicate that the production of IP-10 and Mig by human mesangial cells can be downregulated by NO donors through cGMP-independent inhibition of NF-kappaB activation.

Cells, Cultured↗

PubMedDate not supplied

Anti-cyclic citrullinated peptide antibodies are highly associated with severe bone lesions in rheumatoid arthritis anti-CCP and bone damage in RA.

In the present study we investigated the predictive value of anti-cyclic citrullinated peptide antibodies (anti-CCP) in early rheumatoid arthritis (RA) with respect to the bone damage. Fifty-four patients with early RA (onset <12 months), 35 classified as established RA (onset >12 months), 33 healthy donors and 76 non-RA autoimmune diseases, were enrolled. Anti-CCP and IgG, IgA, IgM rheumatoid factors (RFs) were determined at baseline. Disease activity score (DAS 28) was calculated at the entry. Bone involvement was evaluated by X-rays and sonography. The specificity of anti-CCP was 98.4%; significantly higher than those of the IgM- (86.0%), IgA- (86.0%) and IgG-RFs (66.2%), respectively. Anti-CCP were detected in 23/54 (42.6%) early RA patients and in 16/35 (45.7%) established RA patients. In the early RA group, 6/33 (18.2%) of the patients without bone lesions, 12/16 (75%) with juxta-articular osteoporosis (JO) and 5/5 with joint erosions (JE) resulted positive showing a significant difference between the groups without and with radiological damage. In the established RA group a significant difference being between the group without radiological damage and that with JE was found. Finally, in patients without radiological lesions, examined by ultrasound, anti-CCP antibodies were detected only in subjects with pathologic findings (31.25%). Data here reported confirm that the presence of anti-CCP are specific for diagnosis of RA, of recent onset also and they are potentially useful as prognostic index of bone involvement.

Adult↗

PubMedDate not supplied

["Sarcoidosis-like" granulomatous disease in patients with common variable hypogammaglobulinemia].

Particular attention has been recently dedicated to the development of a sarcoidosis-like form in patients with common variable immunodeficiency (CVI). In sarcoidosis a 5-fold increase in the number of cells in the bronchoalveolar lavage compared with normal controls has been described and the predominance of CD4+ T cells is a common feature. In contrast to patients affected by sarcoidosis or CVI, patients with co-existence of the two diseases had a more favorable prognosis, as progressive pulmonary fibrosis occurred only in a few cases even when persistent alveolar lymphocytosis was present. Moreover, patients presenting with concomitant sarcoidosis and CVI, showed a lower rate of respiratory infections and of the evolution towards bronchiectasies in comparison with patients affected by CVI alone. The clinical evolution observed in our patients was similar with that reported in other studies and confirms their clinical features. One may speculate that the increase in the number of macrophages and T lymphocytes, as suggested by the increased cellularity in the bronchoalveolar lavage of these patients, can produce a peculiar microenvironment characterized by high levels of soluble factors (cytokines). In turn, the latter could be responsible for a more efficacious effector phase of the immune response. This may explain the reduced rate of infectious diseases and consequently of bronchiectasies observed in CVI patients.

Adult↗