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Francesco Liotta

Publications and source records attributed to Francesco Liotta.

18 recordsLinked to original sources
PubMed2007

PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion.

PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biological functions. Recently, the proteic product of a nonallelic variant gene of CXCL4 was isolated from human platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in the mature protein, but exhibits a 38% amino acid divergence in the signal peptide region. We hypothesized that this may imply a difference in the cell type in which CXCL4L1 is expressed or a difference in its mode of secretion. In different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct subcellular localization and a differential regulation of secretion, CXCL4 being stored in secretory granules and released in response to protein kinase C activation, whereas CXCL4L1 was continuously synthesized and secreted through a constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes.

Cells, Cultured↗
PubMed2006

Detection by flow cytometry of ESAT-6- and PPD-specific circulating CD4+ T lymphocytes as a diagnostic tool for tuberculosis.

BACKGROUND: The identification of mycobacteria represents the gold standard in the diagnosis of tuberculosis (TB), but it is not applicable in all patients, and immunological tests, such as the tuberculin skin test (TST), are not specific and sensitive enough. METHODS: By flow cytometry, we measured the CD4 T-cell response to purified protein derivative (PPD) and early secretory antigenic target-6 (ESAT-6) protein using the intracellular cytokine staining technique on whole blood samples obtained from active TB (n = 16), latent TB (n = 17), Bacille Calmette-Guérin (BCG)-vaccinated (n = 11) and healthy (n = 10) donors. All the patients were also tested with conventional TST. RESULTS: The identification by flow cytometry of PPD-specific T lymphocytes upon antigen stimulation of whole blood enables the discrimination of active TB, latent TB and BCG-vaccinated subjects from healthy individuals, whereas the ESAT-6 response discriminated active TB from healthy and BCG-vaccinated individuals. Moreover, this test enables identification of active TB patients who were negative on TST and to distinguish between TB and non-typical mycobacteria TB infections. CONCLUSIONS: The identification by flow cytometry of antigen-specific T lymphocytes upon antigen stimulation of whole blood has a better positive predictive value than TST, and could represent a further tool in the diagnosis of TB infection.

Antigens, Bacterial↗
PubMed2006

Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

AC133 Antigen↗
PubMed2006

Hypergravity speeds up the development of T-lymphocyte motility.

The effect of altered gravity on single cells has been reported in a number of studies. From the investigation of the immune system response to spaceflight conditions, interest has focused on the influence of gravity on single lymphocytes. Microgravity has been shown to decrease lymphocyte activation and to influence motility. On the other hand, the effect of hypergravity on lymphocyte motility has not been explored. We studied the migration of human peripheral blood T lymphocytes cultured in vitro in a hypergravity environment (10g). After hypergravity culture for 1-11 days, T cells were seeded on a fibronectin-coated glass surface, observed by time-lapse bright-field microscopy, and tracked by a computer program. We found that T cells, activated and then cultured in hypergravity, become motile earlier than cells cultured at normal gravity. These results suggest that hypergravity stimulates T cell migration.

Adaptation, Physiological↗
PubMed2006

Redirection of allergen-specific TH2 responses by a modified adenine through Toll-like receptor 7 interaction and IL-12/IFN release.

BACKGROUND: Natural or synthetic ligands of Toll-like receptors (TLRs), such as CpG-containing oligodeoxynucleotides and imidazoquinolines, affect the functional phenotype of antigen-specific human T lymphocytes by inducing cytokine release by cells of the innate immunity. OBJECTIVE: In vitro investigation of the ability of substitute adenines (SAs) to affect antigen-presenting cells and shift the functional phenotype of specific human T(H)2 cells was performed. METHODS: The functional profile of hapten- and allergen-specific T-cell lines obtained in the absence or presence of modified adenines was assessed by means of quantitative real-time PCR, flow cytometry, and ELISAs. Activation of TLRs was evaluated by means of nucleofection of HEK293 cells. RESULTS: The synthetic heterocycle, chemically related to adenine with substitution in positions 2-, 8-, and 9- (SA-2), but not its related derivative lacking 2- and 8- substitutions, stimulated the production of high amounts of IL-12, IL-10, TNF-alpha, and IL-6 by CD14(+) cells and IFN-alpha and CXCL10 by blood dendritic cell antigen (BDCA)-4(+) plasmacytoid dendritic cells. A nuclear factor kappaB-dependent signaling pathway mediated by SA-2 ligation of TLR7 was responsible for these effects. SA-2 also redirected the in vitro differentiation of either Dermatophagoides pteronyssinus group 1 or amoxicillin-specific T(H)2 cells toward the T(H)1/T(H)0 phenotype, with parallel downregulation of GATA-3 and upregulation of T-box expressed in T cells transcription factors. CONCLUSION: Critical substitutions of the adenine backbone confer the ability to activate TLR7, inducing the production of modulatory cytokines able to shift human allergen-specific T(H)2 cells to a T(H)1/T(H)0 phenotype. CLINICAL IMPLICATIONS: Appropriately modified adenines might be used as effective adjuvants for the development of novel immunotherapeutic strategies of allergic disorders.

Adenine↗
PubMed2005

Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells.

Mesenchymal stem cells (MSCs) inhibit the proliferation of HLA-unrelated T lymphocytes to allogeneic stimulation, but the mechanisms responsible for this activity are not fully understood. We show here that MSCs suppress the proliferation of both CD4+ and CD8+ T lymphocytes, as well as of natural killer (NK) cells, whereas they do not have an effect on the proliferation of B lymphocytes. The antiproliferative effect of MSCs was not associated with any effect on the expression of cell-activation markers, induction of cell apoptosis, or mimicry/enhancement of T regulatory cell activity. The suppressive activity of MSCs was not contact-dependent and required the presence of interferon (IFN)-gamma produced by activated T cells and NK cells. Accordingly, even activated B cells became susceptible to the suppressive activity of MSCs in the presence of exogenously added IFN-gamma. The suppressive effect of IFN-gamma was related to its ability to stimulate the production by MSCs of indoleamine 2,3-dioxygenase activity, which in turn inhibited the proliferation of activated T or NK cells. These findings suggest that the beneficial effect on graft-versus-host disease induced by in vivo coinfusion with the graft of MSCs may be due to the activation of the immunomodulatory properties of MSCs by T cell- derived IFN-gamma.

Apoptosis↗
PubMed2005

CD14+CD34low cells with stem cell phenotypic and functional features are the major source of circulating endothelial progenitors.

Endothelial progenitor cells (EPCs) seem to be a promising tool for cell therapy of acute myocardial infarction, but their nature is still unclear. We show here that EPCs obtainable from peripheral blood (PB) derive from the adhesion-related selection in culture of a subset of CD14+ cells, which, when assessed by the highly-sensitive antibody-conjugated magnetofluorescent liposomes (ACMFL) technique, were found to express CD34. These CD14+CD34low cells represented a variable proportion at individual level of CD14+ cells, ranging from 0.6% to 8.5% of all peripheral-blood leukocytes, and constituted the dominant population among circulating KDR+ cells. By using the ACMFL technique, virtually all CD14+ cells present in the bone marrow were found to be CD14+CD34low double-positive cells. EPCs, as well as purified circulating CD14+CD34low cells, exhibited high expression of embryonic stem cell (SC) markers Nanog and Oct-4, which were downregulated in a STAT3-independent manner when they differentiated into endothelial cells (ECs). Moreover, circulating CD14+CD34low cells, but not CD14+CD34- cells, proliferated in response to SC growth factors, and exhibited clonogenicity and multipotency, as shown by their ability to differentiate not only into ECs, but also into osteoblasts, adipocytes, or neural cells. The results of this study may reconcile apparently contradictory data of the literature, showing the generation of PB-derived EPCs from either CD34+ or CD14+ cells. We suggest that the use of this previously unrecognized population of circulating CD14+CD34low cells, which exhibit both phenotypic and functional features of SCs, may be useful in improving cell-based therapies of vascular and tissue damage.

Antigens, CD↗
PubMed2005

Functional features of human CD25+ regulatory thymocytes.

Two families of Treg cells have been described and named "naturally occurring" and "adaptive" regulatory T cells. The naturally occurring Treg cells arise in the thymus, where they achieve their complete functional maturation, whereas the adaptive Treg cells derive from the thymus too, but achieve their functional maturation in the periphery. This review discusses the phenotype and the functional features of the human naturally occurring CD25+ regulatory thymocytes.

Autoimmune Diseases↗
PubMed2005

Thymic regulatory T cells.

Several types of T regulatory (Treg) cells have been described in both mice and humans, including natural or professional (CD4+CD25+ T cells) and adaptive (Th3 and Tr1 cells) Treg cells. The former develops in the thymus and results in an endogeneous long-lived population of self-antigen-specific T cells in the periphery poised to prevent potentially autoimmune reactions. The second subset develops as a consequence of activation of mature T cells under particular conditions of sub-optimal antigen exposure and/or costimulation. Natural Treg cells are positively selected in the cortex through their TCR interactions with self-peptides presented by thymic stromal cells. It is likely that this high-affinity recognition results in signals rendering them anergic and able to produce anti-apoptoptic molecules which protect them from negative selection. Recently, small subsets of CD4+CD25+ and of CD8+CD25+ cells sharing similar characteristics have been detected in human fetal and post-natal thymuses. Both CD4+CD25+ and CD8+CD25+ human thymocytes express Foxp3 and GITR mRNA, as well as surface CCR8 and TNFR2 and cytoplasmic CTLA-4 proteins, which are common features of mature Treg cells. Following activation they do not proliferate or produce cytokines, but express surface CTLA-4 and TGF-beta1. They suppress the proliferation of autologous CD4+CD25- thymocytes to allogeneic stimulation by a contact-dependent mechanism related to the combined action of surface CTLA-4 and TGF-beta leading to the inhibition of the IL-2R alpha chain on target T cells. Lastly, both CD4+CD25+ and CD8+CD25+ Treg thymocytes exert strong suppressive activity on Th1, but much lower on Th2 cells, since these latter may escape from suppression via their ability to respond to growth factors other than IL-2. Treg cells that develop in, and emerge from, the thymus are certainly responsible for the maintenance of self-tolerance and prevention of autoimmune disorders. The result that Th1 cells are highly susceptible to the suppressive activity of Treg thymocytes is consistent with the important role of these cells in protecting against the Th1-mediated immune response to autoantigens.

Animals↗
PubMed2005

CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production.

BACKGROUND: Two variants of the CXCR3 receptor exist, one (CXCR3-A) reactive with CXCL9, CXCL10, and CXCL11 and the other (CXCR3-B) also reactive with CXCL4. Both variants are contemporarily expressed by human T cells. OBJECTIVE: We sought to investigate the in vitro effects of CXCL10 and CXCL4 on the production of TH1 or TH2 cytokines. METHODS: The cytokine profile of antigen-specific human CD4+ T-cell lines obtained in the absence or presence of CXCL10 or CXCL4 was evaluated by means of quantitative RT-PCR, flow cytometry, and ELISA. RESULTS: CXCL10 upregulated IFN-gamma and downregulated IL-4, IL-5, and IL-13 production, whereas CXCL4 downregulated IFN-gamma and upregulated TH2 cytokines. Similar effects were also observed on polyclonally activated pure naive CD4+ T cells. The opposite effects of CXCL10 and CXCL4 on TH1 and TH2 cytokine production were inhibited by an anti-CXCR3 antibody able to neutralize both CXCR3-A and CXCR3-B and were apparently related to the activation of distinct signal transduction pathways. Moreover, CXCL10 upregulated mRNA levels of T-box expressed in T cells and downregulated GATA-3 expression, whereas CXCL4 downregulated T-box expressed in T cells and upregulated GATA-3. Finally, CXCL4, but not CXCL10, induced direct activation of IL-5 and IL-13 promoters. CONCLUSION: CXCL10 and CXCL4 exert opposite effects on the production of human TH1 and TH2 cytokines, likely through their respective interaction with CXCR3-A or CXCR3-B and the consequent activation of different signal transduction pathways. This might represent an internal regulatory pathway of TH cell responses and might contribute to the modulation of chronic inflammatory reactions, including allergy.

CD4-Positive T-Lymphocytes↗
PubMed2004

Matrix metalloproteinase 12-dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis.

OBJECTIVE: Defective angiogenesis, resulting in tissue ischemia, is particularly prominent in the diffuse form of systemic sclerosis (SSc). The present study was undertaken to identify possible differences between normal and SSc microvascular endothelial cells (MVECs) in the expression of the cell-associated urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) system, which is critical in the angiogenic process. METHODS: MVECs were isolated from the dermis of healthy individuals and from the dermis of patients with diffuse SSc. The uPA/uPAR system was examined at the protein and messenger RNA levels. Angiogenesis was assayed on Matrigel-coated porous filters and plates to evaluate cell proliferation, invasion, and capillary morphogenesis. Cleavage of uPAR and the activity of matrix metalloproteinase 12 (MMP-12) were evaluated by Western blotting. RESULTS: Compared with MVECs from healthy skin, MVECs from SSc patients showed higher expression of uPAR. However, in SSc MVECs, uPAR undergoes truncation between domain 1 and domain 2, as shown by flow cytometry, enzyme-linked immunosorbent assay, and Western blotting, a cleavage that is known to impair uPAR functions. These properties of SSc MVECs were associated with poor spontaneous and uPA-dependent invasion, proliferation, and capillary morphogenesis. The uPAR cleavage occurring in SSc MVECs was associated with overexpression of MMP-12. SSc MVEC-conditioned medium impaired uPA-dependent proliferation and invasion as well as capillary morphogenesis in normal MVECs in vitro. Both a general hydroxamate inhibitor of MMP activity and anti-MMP-12 antibodies restored this SSc MVEC-induced impaired functioning. CONCLUSION: Overproduction of MMP-12 by SSc MVECs accounts for the cleavage of uPAR and the impairment of angiogenesis in vitro and may contribute to reduced angiogenesis in SSc patients.

Blotting, Western↗
PubMed2004

High pretransplant serum levels of CXCL10/IP-10 are related to increased risk of renal allograft failure.

In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both acute and chronic rejection. In the present study, pretransplantation sera from 316 cadaver kidney graft recipients were tested for serum CXCL10 and CCL22/MDC levels by an ELISA assay. Kidney graft recipients with normally functioning grafts showed significantly lower serum CXCL10 levels than patients who experienced graft failure, whereas no differences for serum CCL22 levels were observed. After the assignment of all patients to four groups according to serum CXCL10 levels, the death-censored survival rates of grafts were 97.5%, 93.6%, 89.7%, 78.7% (p = 0.0006) at 5 years, while no influence was observed on patient survival. Accordingly, patients with the highest CXCL10 levels showed an increased frequency and severity of rejection episodes. Serum C-reactive protein (CRP) level was also assayed in the same samples. Increase of serum CRP levels represented a predictive parameter for death, but not for graft failure. Multivariate analysis demonstrated that among the analyzed variables, CXCL10 had the highest predictive power of graft loss (RR 2.787). Thus, measurement of pretransplant serum CXCL10 levels might represent a clinically useful parameter to identify subjects who are at high risk of severe rejection and graft failure.

Adult↗
PubMed2003

Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines.

T-cell clones generated from both CD4+CD25+ and CD8+CD25+ human thymocytes were assessed for their ability to suppress the proliferative response to allogeneic stimulation of type 1 T-helper (Th1) or type 2 T-helper (Th2) clones derived from autologous CD4+CD25- thymocytes. Both CD4+ and CD8+ T-regulatory (Treg) cells completely suppressed the proliferation of Th1 clones but exhibited significantly lower suppressive activity on the proliferation of Th2 clones. The partial suppressive effect on Th2 cells was further reduced by the addition in culture of interleukin-4 (IL-4), whereas it was increased in the presence of an anti-IL-4 monoclonal antibody (mAb). The suppressive activity on Th2 clones was also completely inhibited by the addition of IL-7, IL-9, and IL-15 but not of IL-2, whereas the suppressive effect on Th1 clones was only reverted by the addition of IL-15. Of note, Th2 clones expressed significantly higher amounts of mRNA for IL-4 receptor (IL-4R) and IL-9R alpha chains than Th1 clones, whereas the expression of mRNA for IL-2R, IL-7R, and IL-15R alpha chains was comparable. Taken together, these findings demonstrate that Th2 cells have a lower susceptibility than Th1 cells to the suppressive activity of human CD25+ regulatory thymocytes, because they are able to produce, and to respond to, growth factors distinct from IL-2, such as IL-4 and IL-9.

Clone Cells↗
PubMed2003

Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes.

CD8+CD25+ cells, which expressed high levels of Foxp3, glucocorticoid-induced tumor necrosis factor receptor (GITR), CCR8, tumor necrosis factor receptor 2 (TNFR2), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) mRNAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8+CD25+ thymocytes did not produce cytokines, but most of them expressed surface CTLA-4 and transforming growth factor beta1 (TGF-beta1). Like CD4+CD25+, CD8+CD25+ thymocytes suppressed the proliferation of autologous CD25-T cells via a contact-dependent mechanism. The suppressive activity of CD8+CD25+ thymocytes was abrogated by a mixture of anti-CTLA-4 and anti-TGF-beta1 antibodies and it was mediated by their ability to inhibit the expression of the interleukin 2 receptor alpha chain on target T cells. These results demonstrate the existence of a subset of human CD8+CD25+ thymocytes sharing phenotype, functional features, and mechanism of action with CD4+CD25+ T regulatory cells.

Antigens, CD↗
PubMed2003

The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C.

BACKGROUND AND AIMS: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied. METHODS: Expression of CCL21 was assessed by in situ hybridization and immunohistochemistry. CCR7 on T cells was analyzed by flow cytometry. Cultured human HSCs were studied in their activated phenotype. RESULTS: In patients with chronic hepatitis C, expression of CCL21 and CCR7 was up-regulated. CCL21 was detected in the portal tracts and around inflammatory lymphoid follicles, in proximity to T lymphocytes and dendritic cells, which contributed to expression of this chemokine. Expression of CCR7 was also increased in patients with primary biliary cirrhosis. Intrahepatic CD8(+) T lymphocytes isolated from patients with chronic hepatitis C had a significantly higher percentage of positivity for CCR7 than those from healthy controls, and the expression of CCR7 was associated with that of CXCR3. Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model. Exposure of HSCs to CCL21 triggered several signaling pathways, including extracellular signal-regulated kinase, Akt, and nuclear factor kappaB, resulting in induction of proinflammatory genes. CONCLUSIONS: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs.

Cell Movement↗
PubMed2003

The novel synthetic immune response modifier R-848 (Resiquimod) shifts human allergen-specific CD4+ TH2 lymphocytes into IFN-gamma-producing cells.

BACKGROUND: In experimental models, imidazoquinolines exhibit several immunomodulatory activities via Toll-like receptor signaling on cells of the innate immunity. OBJECTIVE: The aim of our study was to investigate whether R-848 (Resiquimod), a small-molecular-weight synthetic compound belonging to the imidazoquinoline family and known for its ability to substantially delay the onset of recurrent genital herpes lesions in both animals and human beings, could influence, at least in vitro, the cytokine production profile of human hapten- or allergen-specific T cells. METHODS: Ampicillin- and Der p 1-specific T-cell lines were derived from peripheral blood of allergic donors in the absence or presence of R-848 and assessed by flow cytometry at the single-cell level for their ability to produce IL-4 and/or IFN-gamma. RESULTS: R-848 induced both hapten- and allergen-specific circulating T cells, including T(H)2 effectors, to produce IFN-gamma and even to lose the ability to produce IL-4, thus shifting their phenotype of cytokine production to a type 0 (T(H)0) or even T(H)1 profile. This effect was associated with an increase in the production of IL-12, IFN-alpha, IL-18, TNF-alpha, IL-10, and IL-15 by CD14(+) cells, as well as an increase in the proportions of IFN-gamma-producing CD3(-)CD16(+) (natural killer) cells. CONCLUSIONS: These results suggest that R-848, and probably other imidazoquinolines, might be used as adjuvants in view of novel allergen-specific immunotherapeutic regimens for the treatment of allergic disorders.

Adjuvants, Immunologic↗
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↗