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A Farre

Publications and source records attributed to A Farre.

16 recordsLinked to original sources
PubMed2006

Alloreaction increases or restores CD40, CD54, and/or HLA molecule expression in acute myelogenous leukemia blasts, through secretion of inflammatory cytokines: Dominant role for TNFbeta, in concert with IFNgamma.

We have previously reported that alloreaction can lead to activation of dendritic cells through secretion of inflammatory cytokines. Here, we addressed whether alloreaction-derived cytokines may also lead to acute myelogenous leukemia (AML) blast differentiation. With this aim, supernatant (sn) harvested from major or minor histocompatibility antigen-mismatched mixed lymphocyte reaction (MLR) were used to culture French American Bristish (FAB) type M4 or M5 AML blasts. Our results showed that the secreted factors induced upregulation of CD40, CD54, and/or HLA molecules in AML blasts. Protein fractionation, blockade experiments and exogenous cytokine reconstitution demonstrated the involvement of TNF in the upregulation of CD54, CD40 and HLA-class II molecules, and of IFNgamma in the increase of HLA-class I and class II molecule expression. But, in line of its much higher levels of secretion, TNFbeta, rather than TNFalpha, was likely to play a preponderant role in AML blast differentiation. Moreover TNFbeta and IFNgamma were also likely to be involved in the AML blast differentiation-mediated by HLA-identical donor T-cell alloresponse against recipient AML blasts. In conclusion, we show herein that upon allogeneic reaction, TNFbeta secretion contributes, in concert with IFNgamma, to increase or restore surface molecules involved in AML blast interaction with T cells.

Adult↗
PubMed2005

Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis.

BACKGROUND: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). AIM: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren's syndrome (SS). SUBJECTS: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). METHODS: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. RESULTS: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. CONCLUSIONS: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

Adolescent↗
PubMed2004

Human mesenchymal stem cells suppress induction of cytotoxic response to alloantigens.

Mesenchymal stem cells (MSC) fail to induce allogeneic responses in mixed lymphocyte reaction assays. Because MSC express HLA class I molecules, here we investigated whether they could be recognized as allogeneic targets by cytolytic T lymphocytes (CTL). With this aim, CTL precursor (CTLp) frequencies were measured following stimulation of T cells with either allogeneic mononuclear cells (MNC) or MSC originated from the same human bone marrow donor. Lysis of MSC was measured at day 10 of culture in standard chromium release assays. In addition, allogeneic PHA blast T cells or B-EBV lymphoblastoid cell lines (LCLs) generated from the same donor were used as positive controls of lysis. Our results showed that when allogeneic MNC were used to stimulate T cells, a high CTLp frequency was detected towards MSC targets. However, when MSC were used as stimulators, CTLp frequencies were markedly altered whatever the targets used, i.e.: MSC, PHA blast T cells or EBV-B LCLs. Moreover, when graded concentrations of MSC were added together with MNC upon stimulation of alloreactive T cells, we observed a dose-dependent decrease in CTLp frequencies towards MSC targets. This inhibition of MSC lysis was partially overcome by adding exogenous rh-IL-2 from the beginning of cultures. In addition, this suppressive effect was totally reproduced when, instead of MSC, supernatant harvested from MSC cultures was added to allogeneic MNC, upon stimulation of alloreactive T cells. In conclusion, our results demonstrate that MSC which can be recognized as targets by pre-activated alloreactive CTLs, may be able to suppress differentiation of CTL precursors into CTL effectors through secretion of suppressive factors.

Cell Differentiation↗
PubMed2002

Cyclosporin A inhibits dendritic cell maturation promoted by TNF-alpha or LPS but not by double-stranded RNA or CD40L.

Here, we investigated the influence of cyclosporin A (CsA) on dendritic cell (DC) generation. With this aim, human DC were propagated from monocytes in serum-free medium with granulocyte macrophage-colony stimulating factor and interleukin-4. DC were then exposed to tumor necrosis factor alpha (TNF-alpha) for maturation. Our results show that CsA does not impair commitment of monocytes into DC, as assessed by loss of CD14 and increase of CD40 and CD1a. However, TNF-alpha-induced DC maturation was affected, as CsA-treated DC expressed lower levels of human leukocyte antigen and costimulatory molecules but sustained levels of CD1a, and less DC expressed DC-lysosomal-associated-membrane-protein (LAMP) and CD83. Accordingly, CsA inhibited the allostimulatory and accessory cell functions of DC. Surprisingly, when other maturation stimuli were used, we observed that CsA significantly inhibited maturation induced by lipopolysaccharides but not by polyribocytidylic acid or CD40 ligand, as assessed by DC phenotype and functions. Therefore, our results indicate that CsA may differentially affect DC maturation.

Antigen Presentation↗
PubMed2001

Generation of helper and cytotoxic CD4+T cell clones specific for the minor histocompatibility antigen H-Y, after in vitro priming of human T cells by HLA-identical monocyte-derived dendritic cells.

BACKGROUND: There is now convincing evidence that minor histocompatibility antigens (mHag) may play a significant role in the pathogenesis of graft-versus-host disease after HLA-identical bone marrow transplantation. Indeed, in this clinical situation, T cells specific for mHag have been isolated. Here, we addressed whether one can generate mHag-specific T cells in vitro, without any in vivo immunization, among healthy blood donors. METHODS: We used monocyte-derived dendritic cells (Mo-DCs) as antigen presenting cells to induce primary responses between healthy HLA-identical siblings, in mixed lymphocyte dendritic cell reactions (MLDCRs). RESULTS: We show that CD4+ T-cell clones, specific for the mHag H-Y, can be generated in vitro. These clones were derived from a gender-mismatched positive MLDCR pair of HLA-identical siblings and were restricted by the HLA DQB1*0502 molecule. In addition, these CD4+ T clones were also able to lyse allogeneic targets with the same pattern of restriction and specificity than helper function. Finally, acute myeloid leukemia (AML) blast cells were susceptible to lysis by these clones. CONCLUSIONS: Altogether, these results predict that Mo-DCs could help to generate class II-associated, mHag-specific, T-cell lines or clones in vitro, between healthy blood donors, without any need of transplantation-mediated immunization.

Acute Disease↗
PubMed1994

Bombesin inhibits growth of pancreatic ductal adenocarcinoma (H2T) in nude mice.

Bombesin (BBS), a tetradecapeptide, stimulates growth of various types of cells, including fibroblasts and human small cell lung cancer, and has been termed the universal "on-switch" due to its ability to stimulate the release of numerous hormones. In addition, BBS receptors have been identified in normal and neoplastic pancreatic tissue. A pancreatic ductal adenocarcinoma cell line (H2T), established in our laboratory, possesses specific binding sites for BBS. The purpose of this study was to examine the effect of BBS on the growth of H2T tumors transplanted into athymic nude mice. H2T cells (5 x 10(6) cells/mouse) were injected s.c. into the interscapular region of the nude mice and then the mice were randomized into two groups (n = 10/group). Mice received either 0.1 ml of saline with 0.1% bovine serum albumin (BSA) (control) or 0.1 ml BBS (5 micrograms/kg) intraperitoneally, three times/day. Tumor area was measured twice weekly until the mice were killed (day 32), when tumor and normal pancreas were removed, weighted, and assayed for DNA and protein content. Administration of BBS significantly inhibited H2T tumor area, weight, and DNA and protein content. Conversely, growth of normal pancreas, removed as an in vivo bioassay so as to ensure the efficacy of BBS, was stimulated. We conclude that BBS is a growth inhibitory factor for H2T tumors and that different mechanisms may be responsible for the differential growth effects elicited by normal and neoplastic pancreas in response to BBS.

Animals↗
PubMed1993

Bombesin stimulates growth of colon cancer in mice and decreases their survival.

Bombesin (BBS) stimulates cellular proliferation of both normal and transformed cells. The mouse colon cancer cells (MC-26) possess specific binding sites for BBS. The purpose of this study, therefore, was to examine the effect of chronic administration of BBS on in vivo growth of MC-26 tumours in Balb/c mice and on survival of tumour-bearing mice. Three groups of mice (n = 10 each) inoculated with MC-26 cells received either saline containing 0.1% bovine serum albumin (BSA), or BBS (5 micrograms kg-1 or 20 micrograms kg-1) dissolved with 0.1% BSA saline by intraperitoneal route three times a day for 15 days. BBS increased weight, DNA and RNA contents of MC-26 tumours. To examine the effect of BBS on survival rates of mice with MC-26 tumours, three groups of mice (n = 20 each) were treated for 31 days, as above. One group of mice inoculated with MC-26 cells received 0.1% BSA saline; the other group of MC-26-inoculated mice and the control group without tumour received BBS (5 micrograms kg-1) dissolved with 0.1% BSA saline. BBS significantly decreased the survival rate of mice bearing MC-26 tumours (median survival; saline group: 42.5 days, BBS group: 32.0 days, P = 0.037). None of the mice in the control group died during the experiment. BBS may stimulate in vivo growth of MC-26 cells through specific receptors.

Animals↗
PubMed1992

Amiloride inhibits the growth of human colon cancer cells in vitro.

Cytoplasmic alkalinization induced by activation of the Na+/H+ antiport plays an essential role in the initiation of cell proliferation. In the present study we examined the effects of amiloride, a specific and reversible inhibitor of Na+/H+ antiporter, on the growth of human colon cancer cells (HT-29). Amiloride (50-800 microM) inhibited the growth of HT-29 cells in a dose-dependent fashion. Forty-three percent inhibition of growth was found at an amiloride concentration of 400 microM after 4 days of treatment. The inhibitory effect of amiloride on growth of HT-29 cells was reversible since removal of amiloride by a media change after 48 h treatment lead to rapid regrowth to control levels. The reversibility of growth inhibition suggests that amiloride is not a non-specific cytotoxin for HT-29 cells. We examined the possible mechanisms for the inhibitory effects of amiloride. Amiloride (400 microM) completely abolished serum-stimulated ODC activity and inhibited difluoromethylornithine (DMFO)-stimulated putrescine uptake by 56%. We conclude that amiloride inhibits the in vitro growth of human colon cancer cells; since ODC-activity and polyamine transport were both inhibited, the inhibitory effects may be mediated in part by polyamine-dependent processes. Amiloride may be a useful agent in the treatment of colon cancer.

Adenocarcinoma↗
PubMed1991

HLA-DRw11, DQw7 has four cellular subtypes revealed by homozygous typing cells and undetected by restriction fragment length polymorphism.

HLA-DRw11 is in strong linkage disequilibrium with DQw7. We have investigated the heterogeneity of DRw11, DQw7 by cellular typing and by HLA cDNA probes. The results obtained by local and other homozygous typing cells in four informative Caucasoid families and 20 genotyped individuals demonstrate the existence of at least four different cellular subtypes. The frequency of DRw11, DQw7 is 25.7% with the following distribution of subtypes: Dw5 (17.3%), JAC (4.2%), JVM (2.8%), TIS (0.7%), and blank (0.7%). JVM (10W 9039) has been previously described; TIS (10W 9042) and JAC are postulated new specificities from our laboratory. None of these subtypes typed for DRw11, DQw1 cells. The cellular heterogeneity contrasts with the absence of polymorphism observed by serology and by restriction fragment length polymorphism after hybridization with DRB, DQA, and DQB probes. Variation in amino acids of the DRB1 chain has been reported for at least three variants: Dw5, JVM, and TIS (more recently).

Amino Acid Sequence↗
PubMed1991

Diversity among DRw13 DQw7 haplotypes as revealed by serology Dw typing and restriction fragment length polymorphism.

HLA-DRw13 is in linkage disequilibrium with DQw6; an unusual association, DRw13 DQw7, is found in 2% of our Caucasoid population. Investigation of genotyped individuals and of families by two allosera and by Dw typing revealed two subtypes: one recognized by homozygous typing cell HAG and by two allosera, the other subtype remained unreactive with both reagents. Analysis of DNA fragments with DNA probes indicated that the HAG-negative subset had DNA fragments in common with DRw6 while the HAG-positive subset shared DNA fragments with DR5. However, all DRw13 DQw7 cells are Dw24 as seen by hybridization with DRB probe.

Genetic Variation↗
PubMed1987

A division of HLA-DQw1 associated with DR1, DR1x-DQw1, DR2 short, DRw10, and DRw14. I. Definition by alloantiserum LY 1327.

We have identified an alloantiserum, LY 1327, directed against part of DQw1-positive cells. This split of DQw1 includes DR1, DR1x, DR2sh, DRw10, and DRw14; the other DQ-associated specificities, -DR2 long and DRw13, are unreactive. Segregation was ascertained in 11 informative Caucasoid families and in 33 genotyped individuals. DR1x refers to a specificity typing as DR blank DQw1, detected by certain anti-DR1 sera and recognized cellularly by HTC DwBON DR blank DQw1 (A. Cambon, Toulouse). Biochemical analysis by two-dimensional gel electrophoresis and DNA analysis by restriction fragment length polymorphism will be discussed since they support the existence of this division of DQw1.

Epitopes↗
PubMed1987

Cellular and serological subtypes of HLA-DR2.

HLA-DR2 and its subtypes were investigated in informative families and unrelated Caucasoid individuals. Serological and cellular typing indicate that DR2 can be divided into DR2 long and DR2 short (sh), each of which can be further subdivided either by HLA-D typing or primed lymphocyte reagents. DR2 long includes Dw2, Dw12 and a new subtype temporarily called D-GEN. The cellular equivalent of DR2sh was recognized by mixed lymphocyte culture (MLC) practised in a family (family FJO); the typing cell individualized was termed FJO. The reactivity of this cell is compared with similar DR2sh varieties described in other laboratories: MN2 (Bach, Minneapolis), AZH (Brautbar, Jerusalem), DB9 (Layrisse, Caracas). The distinction between FJO, MN2 and AZH is not clear, suggesting the existence of shared epitopes; DB9 cells gave typing responses only in family FJO but typed no one else in our panel. Primed cellular reagents FJO anti Dw2 and Dw2 anti FJO when tested against DR2 subtypes support the distinction between DR2 long and DR2sh. The use of these subgroups of DR2 in functional studies, the biochemical analysis of their class II molecules, the pattern of their DNA recombinant fragments and the correlation established with some diseases will be discussed, since they further contribute to the cleavage between DR2 subtypes.

HLA-D Antigens↗
PubMed1983

A possible new HLA-DR allele.

In routine screening of anti-HLA DR reagents, serum 901 was obtained from a woman of negroid origin ten days after delivery of a second child. The spouse was also of black origin. This serum contained polyspecific HLA A and B antibodies. After platelet absorption it reacted with the B cells of 10 out of 119 European Caucasoid panel donors (8.4%) typed for DR1 to DRW10 and for MT1, MT2. Each of these ten donors had only one recognized DR antigen, the other was "blank." Serum 901 gave negative reactions with the homozygous typing cells (HTC) DW1 to DW8. In 18 normal informative Caucasoid families, serum 901 recognized one HLA haplotype in one (or both) parents and segregated with this haplotype in one or more than one child. In one family in which both parents reacted with serum 901, two children were homozygous for this marker and reacted as HTCs. One of these HTCs typed as DW9 and was found to be identical to a DW9.HTC (8W207).

Alleles↗