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Biomedical subjects

F Indiveri

Publications and source records attributed to F Indiveri.

At least 19 recordsLinked to original sources
PubMed2000

Increased beta2-microglobulin-free HLA class I heavy chain serum levels in the course of immune responses to viral antigens and to mismatched HLA antigens.

Besides being present in serum in association with beta2-mu, HLA class I heavy chains are also present in serum as beta2-micro-free moieties. The increase in serum levels of beta2-micro-associated HLA class I heavy chains in conditions associated with an activation of the immune system have prompted us to measure the serum levels of beta2-mu-free HLA class I heavy chains in the course of immune responses to viral antigens and to mismatched histocompatibility antigens. The serum level of beta2-mu-free HLA class I heavy chains, like that of beta2-mu-associated HLA class I heavy chains was significantly increased in patients affected by advanced HIV-1 infection or by chronic hepatitis C (CHC). In the latter group of patients an association was found between a reduction in the beta2-mu-free HLA class I heavy chain serum level and response to therapy with interferon alpha and ribavirin. Moreover, the beta2-mu-free HLA class I heavy chain serum level was increased more than that of beta2-mu-associated HLA class I heavy chains during episodes of liver ischemia following liver transplantation and in the course of acute graft rejection and of acute graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT). These results suggest that the serum levels of beta2-mu-free and beta2-mu-associated HLA class I heavy chains are independently regulated. Furthermore, beta2-mu-free HLA class I heavy chain serum level may be a useful marker to monitor response to therapy in CHC patients and the clinical course of liver and bone marrow grafts.

Adult↗
PubMed2000

Soluble human MHC class I molecules induce soluble Fas ligand secretion and trigger apoptosis in activated CD8(+) Fas (CD95)(+) T lymphocytes.

In the present study, we have evaluated the apoptotic effect of soluble human MHC class I (sHLA-I) antigens on CD8(+) T lymphocytes. sHLA-I antigens and beta(2)-microglobulin-free HLA class I heavy chains, isolated from serum, induced apoptosis on phytohemagglutinin-activated CD8(+) T lymphocytes in autologous and allogeneic combinations. The extent of CD8(+) T cell apoptosis depends on the degree of activation, time of incubation with sHLA-I antigens and amount of sHLA-I antigens added to the cultures. Apoptosis is induced by the interaction of Fas (CD95)(+) cells with soluble Fas ligand which is released following binding of sHLA-I antigens to CD8 molecules. These results suggest that sHLA-I antigens may regulate immune responses by inducing apoptosis in activated CD8(+) T cells.

Apoptosis↗
PubMed1999

Immune regulatory properties of corticosteroids: prednisone induces apoptosis of human T lymphocytes following the CD3 down-regulation.

Glucocorticoid hormones (GCH) induce apoptosis in PHA-primed peripheral blood T lymphocytes (PBL) and down-regulate membrane-bound proteins involved in the immune response. We have analyzed whether GCH are able to affect the expression of the TCR-associated molecules CD3, CD4, and CD8 on PBL-PHA, and whether the modulation of those receptors is related to the GCH-driven apoptosis of the PBL-PHA. Lymphocytes were cultured with PHA or with PHA plus prednisone (PDN) 10(-3), 10(-6), and 10(-9) M. Then expression of CD2, CD3, CD4, CD8, and CD56 antigens was studied by cytofluorimetric assay using propidium iodide (PI) staining and annexin procedure, and by gel electrophoresis of low molecular weight DNA. PDN, at a pharmacological concentration (10(-6) M), was able to inhibit the CD3 expression on T cells. The kinetics of CD3 decrement and of apoptosis show that the down-regulation of CD3 molecules precedes DNA fragmentation and that the cells lacking CD3 are those prone to PDN-induced apoptosis. The inhibition of CD3 is not related to a transcriptional or posttranscriptional phenomenon, because both PBL-PHA and PBL-PHA-PDN expressed the same amount of intracytoplasmic CD3 molecule. PDN also induced a down-regulation of the CD4 and CD8 molecules that resulted sooner in more intense CD8. In vitro PDN is able to induce apoptosis in PBL-PHA through a down-regulation of CD3 molecules.

Adrenal Cortex Hormones↗
PubMed1999

Possible differences in the mechanism(s) of action of different glucocorticoid hormone compounds.

Different glucocorticoid hormones (GCH) show differences in the intensity and in the kinetics of their immunomodulating activity. The mechanism(s) of action of GCH is under investigation, but is has been noted that they exert immune activity via the genomic pathway. We have studied the effects of prednisone (PDN), deflazacort (DFC), and dexamethasone (DXM) on the production of cytokines (IL-2, IL-6, TNF-alpha, IL-10) by peripheral T lymphocytes, and the effects on the inhibition of NF-kB DNA binding activity by activated Jurkat cell line. The data obtained show that the three GCH molecules exert an immunosuppression on cytokine production by T lymphocytes and a strong decrease in the nuclear translocation of NF-kB in Jurkat cells; moreover, (a) not all the cytokines investigated were affected, and not with the same intensity, by the three GCH and (b) DXM inhibited the binding activity of NF-kB less than that of DFC and PDN. These data are in agreement with the concept that different GCH compounds might differ in their binding and affinity properties, tissue-specific metabolism, and interaction with transcription factor.

Adult↗
PubMed1999

IL-15/IL-15R alpha intracellular trafficking in human cells and protection from apoptosis.

IL-15 is an immunostimulatory cytokine sharing with IL-2 the IL-2R beta gamma complex. In vivo, IL-15 detection in synovial fluids has been associated with the development of rheumatoid arthritis. A debate exists as to whether IL-15 has the potential to be secreted in meaningful amounts or to act as a pericellular cytokine. Our data show (1) the presence of two IL-15 isoforms displaying signal peptides of different length and the capacity to be secreted restricted to the isoform bearing the longer one; (2) in cells expressing the two isoforms, the existence of different nuclear localization and intracellular trafficking of IL-15 and IL-15R alpha; and (3) an intercellular microcirculation of IL-15, not detectable with ELISA kits, but displaying a role as an anti-apoptotic factor able to induce the deflection of the TNFR associated factor 2 (TRAF) to IL-15R alpha. Our data point to a juxtacrine mechanism of action of IL-15 and suggest a role for IL-15/IL-15R alpha in the regulation of apoptosis.

Animals↗
PubMed1999

Soluble HLA class I, HLA class II, and Fas ligand in blood components: a possible key to explain the immunomodulatory effects of allogeneic blood transfusions.

The immunomodulatory effect of allogeneic blood transfusions (ABT) has been known for many years. However, a complete understanding of the effects of ABT on the recipient's immune system has remained elusive. Soluble HLA class I (sHLA-I), HLA class II (sHLA-II), and Fas ligand (sFasL) molecules may play immunoregulatory roles. We determined by double-determinant immunoenzymatic assay (DDIA) sHLA-I, sHLA-II, and sFasL concentrations in different blood components. sHLA-I and sFasL levels in red blood cells (RBCs) stored for up to 30 days and in random-donor platelets are significantly (P <.001) higher than in other blood components and their amount is proportionate to the number of residual donor leukocytes and to the length of storage. Blood components with high sHLA-I and sFasL levels play immunoregulatory roles in vitro as in allogeneic mixed lymphocyte responses (MLR) and antigen-specific cytotoxic T-cell (CTL) activity, and induce apoptosis in Fas-positive cells. These data suggest that soluble molecules in blood components are functional. If these results are paralleled in vivo, they should be taken into account in transfusion practice. Blood components that can cause immunosuppression should be chosen to induce transplantation tolerance, whereas blood components that lack immunosuppressive effects should be preferred to reduce the risk of postoperative complications and cancer recurrence.

Adjuvants, Immunologic↗
PubMed1999

The induction of distinct cytokine cascades correlates with different effects of granulocyte-colony stimulating factor and granulocyte/macrophage-colony-stimulating factor on the lymphocyte compartment in the course of high-dose chemotherapy for breast cancer.

The availability of the myeloid hemopoietic growth factors (HGF) granulocyte- and granulocyte/macrophage-colony stimulating factor (G-CSF and GM-CSF) has enhanced the therapeutic index of high-dose chemotherapeutic antitumoral regimens (HDCT), as well as the rate of severe damage to immune competence. We investigated some immune functions before, during and after one course of HDCT for poor-risk breast cancer and compared the effects of G-CSF and GM-CSF on the immune recovery. They exerted different influences on the functions we examined and showed distinctive patterns of both qualitative and quantitative in vivo activities on the immune system. The main findings were that (a) granulocyte and lymphocyte recovery rates were faster in the patients receiving G-CSF; (b) looking at the lymphocyte compartment, this difference was restricted to the CD3(+)/CD8(+) and CD56(+) lymphocyte subsets; (c) the reconstitution rate of CD19(+) lymphocytes was slow in both groups; (d) at the end of follow-up HLA-DR expression by CD3(+) lymphocytes was higher in the GM-CSF group; (e) the lymphocyte proliferative capacity was restored at a faster rate in the GM-CSF group, whereas cytotoxic activities recovered better in the G-CSF group; (f) the early repopulating phase was characterized by higher interleukin-6 serum levels in the GM-CSF group. Overall, GM-CSF seemed to exert an earlier effect on all T lymphocyte subsets, preventing them from a complete drop during the long-lasting "nadir" of the cell count, whereas G-CSF appeared to boost them strongly, though a few days later, hastening their final recovery. The distinct pattern of the cytokine cascade induced by each factor, consistent with the different functional changes, seemed to account for the peculiarities of their immune modulations.

Adult↗
PubMed1999

Beta2-micro-free HLA class I heavy chain levels in sera of healthy individuals. Lack of association with beta2-micro-associated HLA class I heavy chain levels and HLA phenotype.

We have applied a double-determinant immune assay (DDIA) to measure soluble beta2-microglobulin (beta2-micro)-free HLA class I heavy chains in serum. The mean concentration of beta2-micro-free HLA class I heavy chains in serum from 120 healthy subjects was 0.21+/-0.24 microg/ml. The individual serum levels of beta2-micro-free HLA class I heavy chains had a wide distribution, did not seem to be related with HLA phenotype, were stable over time and did not change with age. The serum levels of soluble beta2-micro-free HLA class I heavy chains did not correlate with those of soluble beta2-micro-associated HLA class I heavy chains, suggesting that their release is independently regulated. Three forms of soluble beta2-micro-free HLA class I heavy chains, with apparent molecular masses of 44, 39 and 37-35 kD, respectively, circulate in human serum. These results provide a useful background to assess the serum level of soluble beta2-micro-free HLA class I heavy chains in pathological conditions and to evaluate their putative immunoregulatory function.

Adolescent↗
PubMed1999

Cyclosporin A and iloprost treatment of systemic sclerosis: clinical results and interleukin-6 serum changes after 12 months of therapy.

OBJECTIVES: The main aim was to analyse the long-term therapeutic effects on systemic sclerosis (SSc) patients of treatment with either (i) iloprost alone or (ii) low-dose oral cyclosporin A (CyA) associated with iloprost. A secondary aim was to analyse interleukin-6 (IL-6) serum levels in SSc patients before and after 1 yr of treatment. METHODS: A clinical trial was performed in which 20 consecutive SSc patients were alternately randomized into two homogeneous groups receiving either monthly i.v. iloprost (1 ng/kg/min in 6 h i.v. infusion, for 5 consecutive days, 1 week per month) (Group I) or low-dose CyA (2.5 mg/kg/day) associated with iloprost administration (Group II). IL-6 concentrations were evaluated by ELISA in the sera of each patient before and after 1 yr of therapy and in 20 healthy subjects. RESULTS: After 1 yr of therapy, a significant improvement of skin (P=0.008), microvascular (P=0.004) and oesophageal (P=0.05) morphological and functional parameters was observed only in Group II patients. Furthermore, after 1 yr of treatment, a significant reduction (P=0.007) of IL-6 serum concentration was observed only in Group II patients. CONCLUSIONS: Collectively, our data suggest that the combination of low-dose CyA with iloprost administration may be of clinical utility in SSc and that a mechanism of action of CyA in SSc may include the decrease in IL-6 production.

Adolescent↗
PubMed1998

Acetylcholine-induced, calcium-dependent norepinephrine outflow from peripheral human lymphocytes.

Catecholamines (CA) were studied in peripheral human lymphocytes, as well as in the supernatants, after incubation with L-tyrosine and L-dihydroxyphenylalanine (L-Dopa) for 1 h. The effect that the addition of acetylcholine (ACh), Veratridine, lonomycin or KCI had on the outflow of norepinephrine (NE) from lymphocytes was also studied. The effect of the addition of methoxyverapamil (D600, a Ca2+ channel blocker) and cholinergic antagonists had on the ACh-induced NE outflow was assessed. CA were determined by HPLC-ECD, both in the supernatant and in the cell lysates. L-Tyrosine and L-Dopa significantly (P < 0.01) increased intracellular NE. Neither L-tyrosine, L-Dopa, nor vehicle induced a detectable outflow of NE to the supernatants. ACh [120 microM], Veratridine [100 microM], Ionomycin [10 microM] and KCl [50 mM] (with or without the simultaneous addition of L-tyrosine or L-Dopa) all induced a detectable outflow of NE to the supernatant when added 5 min before the end of incubation. NE was not detectable in the supernatant when the chemicals were added 10 to 20 min before the end of the incubation. When the chemicals were added at lower concentrations, erratic secretion or no secretion whatsoever was observed. D600 [100 microM] was able to significantly (P < 0.01) reduce the ACh-induced NE outflow. Tetraethylammonium (nicotinic antagonist), but not atropine (muscarinic antagonist), significantly (P < 0.001) decreased the ACh-induced NE outflow. The outflow of NE from peripheral human lymphocytes was seen. NE secretion seems to be ACh- and calcium-dependent since Veratridine, Ionomycin and KCl are able to induce Ca2+ entry by means of various mechanisms. The Ca2+ channel blocker employed in this study (D600) reduced the ACh-dependent NE outflow. We can conclude that both ACh (through nicotinic receptors) and calcium are involved in the outflow of NE from peripheral human lymphocytes.

Acetylcholine↗
PubMed1998

IL-15 is produced by a subset of human melanomas, and is involved in the regulation of markers of melanoma progression through juxtacrine loops.

IL-15 is a novel cytokine active through the IL-2R/betagamma. Since several human melanoma cell lines display functional IL-2Rs, we studied the IL-15/melanoma cells interactions. Ten out of 17 melanoma cell lines express the IL-15 transcript and four of them express levels of IL-15 mRNA similar to those detected in control activated monocytes. Nine out of ten cell lines also express two transcripts for the IL-15R alpha originated by the alternative splicing of exon'3'. Two melanoma cell lines, MELP and MELREO, derived from patients with rapidly progressive primary melanomas, co-express the two IL-15 transcripts, originated by alternative splicing of exon 'A'. Intracellular IL-15 protein was only detected in these two cells lines and it is mainly retained in the Endoplasmic Reticulum (ER). However, a small amount of IL-15 is also found in the Golgi apparatus and in the early endosomes, suggesting production and intercellular trafficking of endogenous IL-15 protein. Nevertheless, no biologically active IL-15 could be detected in the supernatant of all melanoma cells. The anti IL-15 blocking mAb M111 causes the up regulation of HLA Class I in dense MELP and MELREO cultures. These data suggest that IL-15 is probably active through juxtacrine loops negatively controlling HLA Class I molecules expression. These data offer, for the first time, a likely explanation to the controversial issue of IL-15 secretion and constitute a natural model for understanding IL-15 routing. Moreover, we identify a subset of melanoma cells producing IL-15, possibly involved in tumor escape mechanisms.

Biomarkers, Tumor↗
PubMed1998

Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation.

CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.

Animals↗
PubMed1998

Immunoregulatory role of soluble HLA molecules: a new skin for an old subject?

The available evidence suggests that measurement of the level of total sHLA-1 antigens and of donor-derived and recipient-derived allospecificities as well as the characterization of their variants in recipient's serum may provide useful information to differentiate graft rejections from infections in allograft recipients. Moreover, a significant progress has been made in our understanding of the functional properties of sHLA-I antigens in serum and of their potential role in the modulation of immune responses. If these preliminary results will be confirmed, then sHLA-I antigens are likely to become important reagents to monitor and treat graft recipients.

Histocompatibility Antigens Class I↗
PubMed1997

Downregulation of HLA class I antigen expression in CD4+ T lymphocytes from HIV type 1-infected individuals.

The expression of HLA class I antigens is downregulated in CD4+ T cells following in vitro HIV-1 infection. We determined whether the expression of HLA class I antigens is downmodulated in peripheral blood lymphocytes (PBLs) of HIV-1-positive subjects and whether this defect correlates with disease progression. A cohort of 62 HIV-1-seropositive individuals in different stages of disease was studied. Among these, four subjects were evaluated at yearly intervals for 6 years. The expression of HLA class I, HLA class II, and CD38 antigens was analyzed in PBLs and in CD4+ and CD8+ T lymphocyte subpopulations. The percentage of HLA class I-positive cells and the membrane density of HLA class I antigens were significantly lower in PBLs from HIV-1-positive individuals than in PBLs from HIV-negative controls, proportionally decreased with disease progression, and significantly correlated with the decrease in CD4+ T lymphocytes. Furthermore, the percentage of HLA class I-positive cells and the membrane density of HLA class I antigens were significantly lower in CD4+ T lymphocytes from AIDS patients with respect to CD4+ T lymphocytes from HIV-negative controls and to CD8+ T lymphocytes from HIV-negative controls and AIDS patients. By contrast, the expression of HLA class II and CD38 antigens was upregulated in CD4+ and CD8+ T lymphocytes from HIV-1-positive subjects. The defective expression of HLA class I antigens could impair the lysis of HIV-infected CD4+ cells by virus-specific HLA class I-restricted cytotoxic T lymphocytes and contribute to the progression of disease.

Adult↗
PubMed1997

Soluble HLA class I and class II molecule levels in serum and cerebrospinal fluid of multiple sclerosis patients.

Increased concentrations of soluble HLA class I and class II molecules (sHLA-I and sHLA-II) have been observed in infectious, inflammatory, and autoimmune diseases. Because autoimmune mechanisms are considered to play a role in the pathogenesis of multiple sclerosis (MS), we decided to dose sHLA-I and sHLA-II in serum and cerebrospinal fluid (CSF) of MS patients comparing their concentrations with those observed in serum and CSF of patients with other neurologic diseases (OND) without evidence of neuroradiologic involvement of central nervous system (CNS) and in serum of healthy donors. The serum concentrations of sHLA-I were higher in both MS and OND patients than in healthy donors (P < 0.05) whereas sHLA-II serum concentrations were lower in MS patients than in both OND patients and healthy donors (P < 0.01). Detectable amounts of sHLA-II were observed in the CSF of 45% of MS patients and in CSF of only 6% of OND patients (P < 0.001). In MS patients a significant correlation between sHLA-I serum and CSF concentrations was observed (P < 0.01), whereas sHLA-II serum and CSF levels did not correlate. In conclusion, alterations of sHLA-I and sHLA-II serum and CSF concentrations are present in MS patients and could be involved in the induction of enhanced susceptibility to develop MS or in MS pathogenesis.

Adolescent↗
PubMed1997

The presence of posttransplant HLA-specific IgG antibodies detected by enzyme-linked immunosorbent assay correlates with specific rejection pathologies.

Posttransplant monitoring of anti-HLA antibodies with routine techniques gives unsatisfactory results due to a variety of technical limitations. We investigated how a new alternative technique correlates with posttransplant clinical events. A total of 313 nonselected serum samples from 136 patients were screened by an ELISA utilizing captured soluble HLA class I antigens. We observed the absence of anti-HLA antibody production in acute rejection cases responding to standard antirejection therapy. On the other hand, we showed a clear presence of these antibodies in acute rejection episodes not responding to standard therapy (P<0.0001) and in chronic rejection (P<0.001). We conclude that routine posttransplant monitoring by ELISA offers early risk assessment that is crucial for proper immunosuppression and for antirejection therapy choice.

Cytotoxicity, Immunologic↗