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Biomedical subjects

F Sallusto

Publications and source records attributed to F Sallusto.

At least 19 recordsLinked to original sources
PubMed2002

Prognostic value of a combination of IPSS, flow rate and residual urine volume compared to pressure-flow studies in the preoperative evaluation of symptomatic BPH.

OBJECTIVE: Evaluate the predictive value of a combination of IPSS, uroflowmetry and ultrasound determination of residual urine volume in the determination of bladder outflow obstruction (BOO) and in predicting treatment outcome. METHODS: Forty-five out of a group of 60 BPH symptomatic patients were included. Preoperative evaluation: urine culture, PSA, uroflowmetry with sonographic measurement of post-void residual urine, DRE, IPSS with quality of life questions and pressure-flow study. Selection criteria for surgery were IPSS > 16 and Qmax < 10 ml/s. Transurethral resection of the prostate was performed in these patients; the control visit was performed at 3 months. Treatment success was defined as Qmax above 15 ml/s, residual urine of less than 100 ml, a 50% reduction in IPSS and absence of urinary retention. RESULTS: Urodynamic abnormalities were found in 42 patients (93.3%): 19 had detrusor instability, 5 patients showed impaired contractility, 37 patients had proven BOO, and 8 patients were unobstructed or mildly obstructed. The overall success rate was 86% when measured by the IPSS. Its preoperative value was 16.9, and dropped significantly to 4 (P = 0.005). The score improved significantly after surgery only in the obstructed group compared to the non-obstructed group (P = 0.001), however preoperative IPSS did not correlate with objective treatment results. CONCLUSIONS: A high proportion of patients successfully operated (71.1%) had a combination of IPSS > 16 and Qmax < 10 ml/s, although BOO could not be accurately predicted with non-invasive methods alone. Patients with no or mild infravesical obstruction had only minimal improvement of IPSS and uroflowmetry following surgery.

Aged↗
PubMed2001

Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells.

Memory T lymphocytes proliferate in vivo in the absence of antigen maintaining a pool of central memory T cells (T(CM)) and effector memory T cells (T(EM)) with distinct effector function and homing capacity. We compared human CD4(+) naive T, T(CM), and T(EM) cells for their capacity to proliferate in response to cytokines, that have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded with very high efficiency T(EM), while T(CM) were less responsive and naive T cells failed to respond. Dendritic cells (DCs) and DC-derived cytokines allowed naive T cells to proliferate selectively in response to IL-4, and potently boosted the response of T(CM) to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rbeta and the common gamma chain (gamma(c)). The extracellular signal regulated kinase and the p38 mitogen-activated protein (MAP) kinases were selectively required for TCR and cytokine-driven proliferation, respectively. Importantly, in cytokine-driven cultures, some of the proliferating T(CM) differentiated to T(EM)-like cells acquiring effector function and switching chemokine receptor expression from CCR7 to CCR5. The sustained antigen-independent generation of T(EM) from a pool of T(CM) cells provides a plausible mechanism for the maintenance of a polyclonal and functionally diverse repertoire of human CD4(+) memory T cells.

CD4-Positive T-Lymphocytes↗
PubMed2001

Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.

The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 cross-linking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells. (Blood. 2001;98:533-540)

Antigen Presentation↗
PubMed2001

Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells.

Following encounter with pathogens, dendritic cells (DC) mature and migrate from peripheral tissues to the T cell areas of secondary lymphoid organs, where they produce regulatory cytokines and prime naive T lymphocytes. We investigated in two subsets of human peripheral blood DC the expression of Toll-like receptors (TLR1 through TLR9) and the regulation of chemokine receptors and cytokine production in response to different maturation stimuli. Myeloid DC express all TLR except TLR7 and TLR9, which are selectively expressed by plasmacytoid DC. Myeloid and plasmacytoid DC respond to pathogen-associated molecular patterns according to their TLR expression. In response to the appropriate stimuli both DC types up-regulate CCR7, a receptor that drives DC migration to the T cell areas. Type I IFN was produced only by plasmacytoid DC and at early time points after stimulation. Furthermore, its production was elicited by some of the maturation stimuli tested. These results reveal a remarkable specialization and complementarity in microbial molecule recognition as well as a flexibility in effector function among myeloid and plasmacytoid DC.

Cytokines↗
PubMed2001

The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics.

Dendritic cells are responsible for directing different types of T cell responses, from thymic negative selection to the generation of effector and memory cells and the induction of peripheral tolerance. Recent studies indicate that the dendritic cell lineage, the extent of recruitment into inflamed tissues and migration to lymph nodes, the nature of maturation stimuli and the kinetics of activation have a quantitative and qualitative impact on T cell stimulation, thus exerting an instructive control on T cell responses.

Animals↗
PubMed2001

Antigen decoding by T lymphocytes: from synapses to fate determination.

Naïve T lymphocytes sense foreign antigens by establishing contacts with dendritic cells (DCs). At the immunological synapse between the T cell and a DC, T cell receptors (TCRs) are serially engaged and triggered by specific ligands. The amount and duration of TCR triggering and the efficiency of signal amplification determine T cell commitment to proliferation and differentiation. The nature and availability of DCs bearing antigen and costimulatory molecules shape the T cell response, giving rise to distinct functional outputs such as effector and memory T cell generation or T cell tolerance.

Animals↗
PubMed2001

Kinetics of GATA-3 gene expression in early polarizing and committed human T cells.

Different transcription factors have been shown to control the transition of naive T cells into T helper 1 (Th1)/Th2 subsets. The T-cell-specific transcription factor GATA-3 is known to be selectively expressed in murine developing Th2 cells and to exert a positive action on Th2-specific cytokine production. Investigating GATA-3 gene regulation in human T cells we have found that naive T cells highly express GATA-3, and during early T2 or T1 polarization, respectively, they either maintain or quickly down-regulate expression. In developing T2 cells, as well as in committed Th2 cell lines and clones, we found a positive correlation among GATA-3, interleukin (IL)-5 and IL-4 gene expression kinetics, supporting the positive action of GATA-3 on Th2-specific cytokine production. A possible relationship between GATA-3 gene expression and the down-regulation of the IL-12 receptor (beta2-chain; IL-12Rbeta2) gene was evident only in the early phases of T2 polarization (within 24 hr), and not demonstrated at later times. During T-cell commitment the presence of IL-4 in the culture was essential to maintain or enhance GATA-3 transcription, while IL-12 was not necessary for full repression of GATA-3. Finally, we showed selective GATA-3 up-regulation in human Th2 cell lines and clones and the maintainance of a low basal level of GATA-3 expression in Th1 cells upon activation.

Cell Differentiation↗
PubMed2001

Origin and migratory properties of dendritic cells in the skin.

The professional antigen presenting cells of the skin, namely Langerhans cells and dermal dendritic cells, are continuously exposed to environmental stimuli. The population of antigen-carrying dendritic cells that migrates from this site to the draining lymph nodes is highly dynamic, and its density, composition and function changes as a consequence of dendritic cell recruitment and activation in tissues, as well as interactions with T lymphocytes in the specialized lymph node microenvironments. Therefore dendritic cells within the skin are the key regulators of both quantitative and qualitative aspects of immune responses to local antigenic challenge.

Animals↗
PubMed2001

Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma.

PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.

Antigens, Neoplasm↗
PubMed2000

Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production.

Chemokines and their receptors have been identified as major regulators controlling the functional organization of secondary lymphoid organs. Here we show that expression of CXC chemokine receptor 5 (CXCR5), a chemokine receptor required for B cell homing to B cell follicles, defines a novel subpopulation of B helper T cells localizing to follicles. In peripheral blood these cells coexpress CD45RO and the T cell homing CC chemokine receptor 7 (CCR7). In secondary lymphoid organs, CD4(+)CXCR5(+) cells lose expression of CCR7, which allows them to localize to B cell follicles and germinal centers where they express high levels of CD40 ligand (CD40L), a costimulatory molecule required for B cell activation and inducible costimulator (ICOS), a recently identified costimulatory molecule of the CD28 family. Thus, when compared with CD4(+)CD45RO(+)CXCR5(-) cells, CD4(+)CD45RO(+)CXCR5(+) tonsillar T cells efficiently support the production of immunoglobulin (Ig)A and IgG. In contrast, analysis of the memory response revealed that long-lasting memory cells are found within the CD4(+)CD45RO(+)CXCR5(-) population, suggesting that CXCR5(+)CD4 cells represent recently activated effector cells. Based on the characteristic localization within secondary lymphoid organs, we suggest to term these cells "follicular B helper T cells" (T(FH)).

Antibody Formation↗
PubMed2000

A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response.

In a significant proportion of melanoma patients, CTL specific for the melan-A(26/7-35) epitope can be detected in peripheral blood using HLA-A2/peptide tetramers. However, the functional capacity of these CTL has been controversial, since although they prove to be effective killers after in vitro expansion, in some patients they have blunted activation responses ex vivo. We used phenotypic markers to characterize melan-A tetramer(+) cells in both normal individuals and melanoma patients, and correlated these markers with ex vivo assays of CTL function. Melanoma patients with detectable melan-A tetramer(+) cells in peripheral blood fell into two groups. Seven of thirteen patients had a CCR7(+) CD45R0(-) CD45RA(+) phenotype, the same as that found in some healthy controls, and this phenotype was associated with a lack of response to melan-A peptide ex vivo. In the remaining six patients, melan-A tetramer(+) cells were shifted toward a CCR7(-) CD45R0(+) CD45RA(-) phenotype, and responses to melan-A peptide could be readily demonstrated ex vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells were examined, a similar dichotomy emerged. These findings demonstrate that activation of melan-A-specific CTL occurs in only some patients with malignant melanoma, and that only patients with such active immune responses are capable of responding to Ag in ex vivo assays.

Adult↗
PubMed2000

Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells.

The immune response is initiated in organized lymphoid tissues where antigen-loaded dendritic cells (DCs) encounter antigen-specific T cells. DCs function as packets of information that must be decoded by the T cell before an appropriate immune response can be mounted. We discuss how the dynamics of DC-T cell encounter and the mechanism of T cell differentiation make the decoding of this information stochastic rather than determinate. This results in the generation of both terminally differentiated effector cells and intermediates that play distinctive roles in protection, immunoregulation, and immunological memory.

Animals↗
PubMed2000

Cholera toxin induces maturation of human dendritic cells and licences them for Th2 priming.

Cholera toxin (CT) is a potent mucosal adjuvant that amplifies B and T cell responses to mucosally co-administered antigens, stimulating predominant Th2-type responses. However, little is known about the mechanism of adjuvanticity of CT and on the influence this toxin may have on Th2 cell development during the priming of an immune response. We analyzed the effect of CT on dendritic cells (DC), which are responsible for the priming of immune responses at the systemic as well as at the mucosal level. We found that CT induces phenotypic and functional maturation of blood monocyte-derived DC. Indeed, CT-treated DC up-regulate expression of HLA-DR molecules, B7. 1 and B7.2 co-stimulatory molecules, and are able to prime naive CD4(+)CD45RA(+) T cells in vitro, driving their polarization towards the Th2 phenotype. Furthermore, CT-matured DC express functional chemokine receptors CCR7 and CXCR4 which may render them responsive to migratory stimuli towards secondary lymphoid organs. Interestingly, the maturation program induced by CT is unique since CT does not induce but rather inhibits cytokine (IL-12p70 and TNF-alpha) and chemokine (RANTES, MIP-1alpha and MIP-1beta) secretion by lipopolysaccharide- or CD40 ligand-activated DC. Our results help to elucidate the mechanism of action of CT as an adjuvant and highlight a new stimulus of bacterial origin that promotes maturation of DC.

Adult↗
PubMed2000

A flavonoid sulfate antigen activates human alphabeta CD8+ Th2 lymphocytes in pollen allergy.

Cellular immune responses are initiated when T lymphocytes expressing alphabeta TCR recognize peptide antigens bound to MHC molecules or, less frequently, double-stranded glycolipid antigens bound to CD1 molecules. In the allergy to Parietaria judaica, human alphabeta CD8+ Th2 lymphocytes react to a non-peptide pollinic antigen presented by B cells. The environmental allergen was purified and identified as a new flavonoid pigment: 2'-O-sulfate, 6-O-betaD-glucuronopyranosyl, 2',5,6-trihydroxy-isoflavone. Its specific recognition by alphabeta CD8+ Th2 T cells (1) depends upon an MHC- and CD1-independent presentation mediated by B cells, (2) is determined by the flavonoid carbohydrate and sulfate groups and (3) leads to positive skin prick test in allergic patients. Hence, an unusual mode of aromatic sulfated antigen recognition by alphabeta CD8+ Th2 T lymphocytes might underlie the cellular mediation of human allergy to plant allergens.

Allergens↗
PubMed2000

From synapses to immunological memory: the role of sustained T cell stimulation.

T cell activation is a sustained process driven by antigen and cytokines, which results in the generation of large numbers of effector and memory cells. Recent experiments from different fields have shed light on the mechanisms that maintain the signaling process at the level of a single synapse between a T cell and an antigen-presenting cell, as well as at the level of a secondary lymphoid organ, in the course of the immune response. These findings explain the unique capacity of the immune system to discriminate between antigens from infectious and noninfectious agents.

Cell Movement↗