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M Jeddi-Tehrani

Publications and source records attributed to M Jeddi-Tehrani.

At least 19 recordsLinked to original sources
PubMed2004

The distribution of Entamoeba histolytica and Entamoeba dispar in northern, central, and southern Iran.

The present study was carried out from August 1999 through February 2002 in order to determine the prevalence of Entamoeba histolytica and Entamoeba dispar in three different climatic regions of Iran by using a PCR-RFLP method. A total of 16,592 stool samples were randomly collected from different age-groups in central, northern, and southern Iran in both urban and rural areas. The samples were examined by direct and formalin-ether concentration methods. A total of 226 samples were positive for E. histolytica/E. dispar cysts. Of these, 101 isolates were cultured and maintained successfully in Robinson's medium and were identified by the PCR-RFLP method. The study showed that 92.1% of isolates were E. dispar and 7.9% were E. histolytica or mixed infections. The ratio of E. histolytica to E. dispar was higher in southern regions (tropical and subtropical) than in the other two regions. This study demonstrated that E. dispar is the predominant species found among "cyst passers" in Iran.

Animals↗
PubMed2004

Identification of cross-reactive and restricted epitopes localized on human chorionic gonadotropin beta-subunit by monoclonal antibodies.

Human chorionic gonadotropin (hCG) belongs to the family of glycoprotein hormones. All members of the family are composed of an identical alpha subunit and structurally related beta subunit which confers biological specificity. Specific quantification and functional analysis of hCG require the use of monoclonal antibodies recognizing different epitopes of hCGbeta. This study describes the production and characterization of monoclonal antibodies (MAbs) to hCGbeta with no cross-reactivity to other glycoprotein hormones. Spleen cells from Balb/c mice immunized with hCG were fused with mouse SP2/0 myeloma cells. Fused cells were grown in hypoxanthine, aminopterine, and thymidine (HAT) selective medium and cloned by limiting dilution assay. Antibody-secreting cells were screened by enzyme-linked immunosorbent assay (ELISA) and the specificity of secreted MAbs was further analyzed, using a panel of highly purified and recombinant glycoprotein hormones, their subunits and peptides representing the C-terminal end of hCGbeta (hCGbeta-CTP) by ELISA and immunoblotting. The affinity constant (K(aff)) was also determined by ELISA. Three murine hybridomas designated G5M1, B12M2 and F4M3 were obtained that secrete MAbs specific for hCGbeta. The G5M1 MAb reacts only with hCGbeta, hCGbeta-CTP and intact hCG with no detectable cross-reaction with hCGalpha or any of the other glycoprotein hormones. The specificity of B12M2 MAb is very similar to G5M1, but it does not react with hCGbeta-CTP. The F4M3 MAb also has similar specificity to G5M1 and B12M2, but it strongly cross-reacts with hLH. The affinity constant (Kaff) of G5M1, B12M2 and F4M3 was found to be 4.28 x 10(9), 5.2 x 10(8), and 1.97 x 10(9) M(-1), respectively. Our results indicate that G5M1 and B12M2 MAbs are specific for hCG and recognize epitopes restricted to hCGbeta, but F4M3 recognizes a common epitope expressed both on hCGbeta and hLHbeta.

Animals↗
PubMed2003

Analysis of T-cell receptor beta chain variable gene segment usage in healthy adult responders and nonresponders to recombinant hepatitis B vaccine.

One to 10 per cent of healthy adult individuals do not produce protective levels of anti-hepatitis B surface (HBs) antibodies, following a standard vaccination protocol. Lack of an HBs antigen (Ag)-specific T-cell repertoire is amongst the possible defects, which may lead to humoral unresponsiveness and is the main objective of this study. We analysed TcR BV (T-cell receptor beta chain variable) gene usage in T lymphocytes from nine healthy adult responders and six nonresponders to recombinant HB vaccine, before and after booster vaccination. CD4+ and CD8+ T-cell populations were isolated from peripheral blood mononuclear cells by magnetic beads, and the expression of TcR BV genes in each population was investigated by reverse transcription polymerase chain reaction and hybridization with specific probe. When the usage of each TcR BV gene within CD4+ and CD8+ T cells of the responders was compared with that of nonresponders, statistically significant difference (P < 0.01) was noted for BV5S2-3 gene family in CD4+ T cells of nonresponders. Furthermore, individual vaccinees were shown to overexpress several TcR BV genes. To characterize the T-cell repertoire and determine their clonal nature, analysis of CDR3 length polymorphism was performed. Our results show that T-cell response to HBsAg is generally oligoclonal and involves multiple BV families. Furthermore, overexpressed individual TcR BV genes and CDR3 length distributions in response to HBsAg are subject-dependent. In conclusion, our results are not in line with the notion that defective TcR repertoire may be an explanation for unresponsiveness to recombinant HBsAg vaccine.

Adult↗
PubMed2003

Kinetics of cytokine gene expression in human CD4+ and CD8+ T-lymphocyte subsets using quantitative real-time PCR.

The time kinetics of five cytokines [interleukin-2 (IL-2), IL-5, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha)] and one cytotoxic effector protein (granzyme B) was analysed by real-time quantitative polymerase chain reaction (PCR) following in vitro stimulation of human CD4 and CD8 T lymphocytes. Two stimuli were used, a mitogen [phytohemagglutinin (PHA)] and a recall antigen [purified protein derivative (PPD)]. The pattern of cytokine mRNA expression was found to be dependent on the T-cell subset and stimulus used. A wide interindividual variability in the cytokine gene expression pattern was demonstrated. Two expression patterns were observed. A bell-shaped expression profile was seen for most cytokines upon PHA activation in both subsets and PPD-activated CD4 T cells, whereas a biphasic/multiphasic expression pattern was noted in CD8 T cells upon PPD stimulation. For most cytokines, the time to induction was within 30 min of activation, and maximum accumulation seemed to be obtained after 4-8 h of activation. A sustained high level could, however, be noticed for up to 24 h. Granzyme B gene expression was also induced within 30 min of activation but showed a continuous gradual increase and late maximal accumulation (48-72 h). The findings of the present study are of importance when designing studies using the cytokine gene expression profile as a marker for antigen-specific T lymphocytes. It might be recommended that cytokine gene expression (IL-2, IL-5 and IFN-gamma) should be measured after 4-8 h of specific activation but also up to 24 h of stimulation is acceptable. Granzyme B should preferentially be measured after 48-72 h of activation.

CD4-Positive T-Lymphocytes↗
PubMed2003

Characterization of human hybridoma clones isolated from hemophilia patients with specificity for different domains of coagulating factor VIII.

Hemophilia A patients treated with human coagulating factor VIII (FVIII) may develop inhibitory antibodies (inhibitors). Characterization of the inhibitors at the clonal level may help exploring new therapeutic strategies. We have generated lymphoblastoid cell lines (LCLs) producing anti-FVIII antibodies from peripheral blood lymphocytes of hemophilia A patients with high inhibitor titers. We fused the anti-FVIII-positive LCLs with a heteromyeloma, to produce FVIII specific hybridomas. We determined the specificity, isotype, idiotypic and immunoglobulin (Ig) variable region heavy (VH) chain gene family profiles of the secreted antibodies (Ab) by ELISA, immunoblotting and RT-PCR. We established eight hybridomas which produced high titers of anti-FVIII Ab. All hybridomas secreted IgM Ab, associated with either kappa(5/8) or lambda(3/8) light chain. Analysis of the expressed VH genes by RT-PCR revealed that the hybridomas utilized only the VH1 (63%) or the VH3 (37%) gene families. Among the cross-reactive idiotypes (CRIs) we tested, only the VH1 and VK3b-associated CRIs were expressed by 3 hybridomas. Immunoblotting of thrombin-digested FVIII demonstrated distinct patterns of reactivity of the monoclonal Ab (MAb) secreted by the hybridomas, which recognized either the A2 domain of the Fvm heavy chain, or the light chain, or both. Our findings suggest that: a) the isotype of the anti-FVIII Ab secreted by LCLs and hybridoma clones (IgM) differs from that of anti-FVIII Ab in vivo, which are predominantly IgG4: this suggests a negative selection of the isotype-switched FVIII-specific B-cells in the periphery of these patients; b) the anti-FVIII Ab have a biased representation of the VH1 gene family, and c) somatic mutations in the VH genes coding for FVIII specificity occur in the anti-FVIII Ab response, as evidenced by lack of expression of the VH-associated CRI.

Autoantibodies↗
PubMed2002

Diminished Th1 and Th2 cytokine production in healthy adult nonresponders to recombinant hepatitis B vaccine.

Vaccination of healthy adults with recombinant hepatitis B (rHB) vaccine fails to induce a protective antibody response in a proportion of individuals. Imbalanced T-helper (Th)1/Th2 response has been attributed to the lack of specific antibody response to rHB vaccine. In this study, in vitro production of interleukin (IL)-2, interferon (IFN)-gamma and IL-10 was investigated in Iranian healthy adults vaccinated with rHB vaccine. Peripheral blood mononuclear cells (PBMC) were isolated from 18 high responders and eight nonresponders and stimulated with rHB antigen or phytohaemaglutinin (PHA) mitogen. The cytokines were quantitated in culture supernatants by sandwich enzyme-linked immunosorbent assay (ELISA). Our results demonstrated a significant decrease in the production of IL-2, IFN-gamma and IL-10 (P < 0.005) in response to rHB antigen. The levels of all cytokines induced by PHA were similarly represented in both groups of vaccinees. These findings suggest that unresponsiveness to rHB vaccine may be owing to inadequate Th1- and Th2-like cytokine production.

Adult↗
PubMed2001

Dendritic cells in patients with non-progressive B-chronic lymphocytic leukaemia have a normal functional capability but abnormal cytokine pattern.

Dendritic cells (DC) are attractive candidates for use in vaccine-based immunotherapy. We have analysed the functional capability of DC generated in vitro from blood CD14(+) cells of chronic lymphocytic leukaemia (CLL) patients and healthy donors by culturing for 10 d with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumour necrosis factor-alpha (TNF-alpha). Two distinct DC populations were identified in patients as well as in controls. The majority of DC expressed CD11c and a minority also CD123. Most of the DC generated from both patients and controls exhibited a mature phenotype indicated by CD83 and major histocompatibility complex (MHC) class II expression, as well as by a characteristic morphology. Less than 1% of DC exhibited CD14. CLL DC had a similar expression of accessory molecules (CD54, CD80 and CD86) as control DC. The mean fluorescence intensity of CD80 and MHC class I molecules was significantly higher on CLL DC than on control DC (P < 0.05). At the gene level (real-time polymerase chain reaction) the expression of IL-10 was higher in CLL (P = 0.028) than in control DC. IL-1 beta and IL-12p(35) transcripts were also more abundant in CLL than in control DC but did not reach statistical significance. The expression of IL-4 and TNF-alpha was similar to that of control DC. The interferon gamma (IFN-gamma) gene expression level in CLL DC was decreased compared with control DC. DC of CLL patients had a similar capacity to stimulate in mixed leucocyte reaction as well as to present a recall antigen (PPD) as control DC. Thus, DC of CLL patients seem to have a normal function and may serve as antigen preserving cells for presentation of tumour antigens in a therapeutic vaccination approach. The mechanisms behind the observed increase in some surface molecules and the abnormal cytokine profile of CLL DC is not clear but might indicate pre-activation of DC in vivo, which may have a regulatory role in the pathobiology of CLL.

Aged↗
PubMed2000

Autologous T lymphocytes recognize the tumour-derived immunoglobulin VH-CDR3 region in patients with B-cell chronic lymphocytic leukaemia.

We have previously shown that autologous T cells recognize leukaemic cells from patients with chronic lymphocytic leukaemia (B-CLL) in an MHC class I- and/or II-restricted manner. A candidate recognition structure might be the tumour cell-derived Ig VH complementarity-determining region (CDR)3. Three patients with B-CLL were analysed for the presence of autologous T cells recognizing the tumour-specific VH-CDR3 region. The VH region was shown to be mutated in all three patients. In two patients, a VH-CDR3-specific T-cell response was detected by proliferation assay, as well as by gamma-interferon (IFN) production. The responses could be inhibited by monoclonal antibodies against MHC class II, but not MHC class I. In the third patient, a VH-CDR3 proliferative response was detected, which could be inhibited by an anti-MHC class I monoclonal antibody, but not by anti-MHC class II antibodies. No gamma-IFN response could be detected in this patient. In no patient was an interleukin (IL)-4 response noted. Thus, in patients with B-CLL, naturally occurring T cells recognizing the tumour-unique VH-CDR3 region are present.

Aged↗
PubMed2000

Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia.

This study analysed a naturally occurring specific cellular immunity against tumour cells in chronic lymphocytic leukaemia (CLL) patients. Five out of eight patients had blood T lymphocytes able to recognize spontaneously and specifically the autologous tumour B cells (proliferation assay). In these five patients, detection of cytokines by real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was the most abundant cytokine gene expressed by the T cells that recognized the autologous tumour B cells. Other activated cytokine genes were gamma-interferon (IFN), interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha, but not IL-4. This profile suggests a type 1 anti-B-CLL T-cell response. CD80 and CD54 were relatively downregulated on the native tumour B cells compared with control normal B cells. Upregulation of CD80 on the leukaemic cells was mandatory for the induction of such a specific T-cell response. CD80 and CD54 monoclonal antibodies inhibited the specific T-cell DNA synthesis proliferation. The proliferative T-cell response was either MHC class I or class II restricted (inhibition by monoclonal antibodies). The specific cytokine gene expression could be found in isolated CD4, as well as CD8, T-cell subsets. This study demonstrated the presence of a potential natural specific CD4, as well as a CD8 type 1 T-cell immunity against the leukaemic CLL tumour B cells in CLL. A further detailed analysis of the spontaneous anti-CLL T-cell immunity is warranted that may facilitate the development of effective anti-tumour vaccines in CLL.

Adult↗
PubMed1999

Oligoclonal TCRBV gene usage in B-cell chronic lymphocytic leukemia: major perturbations are preferentially seen within the CD4 T-cell subset.

TCRBV (T-cell receptor B variable) gene usage and CDR3 size distribution were analyzed using reverse transcription polymerase chain reaction (RT-PCR) to assess the T-cell repertoire of 10 patients with B-cell chronic lymphocytic leukemia (B-CLL) and in nine age-matched healthy control donors. When the usage of each TCRBV gene within the CD8(+) T cells of the patients was compared with that of the controls, no statistically significant difference was noted except for BV 6S1-3. In contrast, within the CD4(+) T cells of the CLL patients, a statistically significant overexpression for four BV families (2, 3, 5S1, 6S1-3) was seen while an underrepresentation was noted for five BV families (10, 11, 15, 16, 19). Based on the criterion that a value of any BV higher than the mean + 3 standard deviation (SD) of healthy controls indicated an overexpression, individual patients were shown to overexpress several TCRBV genes compared with the controls. Analyses of the CDR3 length polymorphism showed a significantly higher degree of restriction within CD4(+) and CD8(+) T cells of the patients, as compared with the corresponding control T-cell population. There was a significant difference in the CDR3 size distribution pattern with a more polymorphic CDR3 length pattern in the age-matched controls as compared with CLL patients, suggesting different mechanisms driving the T cells towards a clonal/oligoclonal TCRBV usage in patients and controls, respectively. The results show major perturbations of T cells in CLL patients, more frequently seen in the CD4(+) T-cell subset, indicating that nonmalignant CD4(+) T cells may be involved in the pathogenesis of CLL, but also CD8(+) T cells.

Adult↗
PubMed1999

Diverse T-cell receptor CDR3 length patterns in human CD4+ and CD8+ T lymphocytes from newborns and adults.

T cells are essential in the initiation and maintenance of immune responses. Specific interaction between T cells and a presumptive antigen occurs through recognition of an MHC-peptide complex by the T-cell receptor (TCR). The complementarity-determining region (CDR) 3 of the TCR has direct contact with the peptide. Here we describe CDR3 length variability of six different TCRBV gene families of CD4+ and CD8+ umbilical cord (UC) and peripheral blood (PB) T cells. Amplified products spanning the TCR CDR3 regions from CD4+ PB, CD4+ UC and CD8+ UC blood T cells typically displayed Gaussian-like distributions. In contrast, profound and frequent perturbations were recorded in CD8+ PB lymphocytes, with a non-Gaussian pattern in more than half of the samples studied. A substantial portion of the perturbed CD8+ subsets were clonal or oligoclonal, as determined by CDR3-length restriction, TCRBJ gene usage and nucleotide sequencing. This implies that the conditions for shaping and maintenance of the peripheral TCR repertoire are profoundly different for CD8+ and CD4+ T cells.

Adult↗
PubMed1999

Peripheral blood T-cell receptor beta-chain V-repertoire in atopic dermatitis patients after in vitro exposure to Pityrosporum orbiculare extract.

The yeast Pityrosporum orbiculare belongs to the normal cutaneous flora but is also considered to be one of the factors that may contribute to atopic dermatitis (AD). In the present study we investigated the possibility that P. orbiculare can act with superantigen activity in AD. P. orbiculare-reactive T-cell lines (TCLs) were obtained after stimulation of peripheral blood mononuclear cells (PBMC) with P. orbiculare extract. T-cell receptor beta-chain V-segment (TCRBV) usage was investigated using monoclonal antibodies and flow cytometry. We could not find any difference in TCRBV usage between AD patients (n = 10) and healthy controls (n = 5), either in fresh PBMC or in P. orbiculare-reactive TCLs. Compared with their original PBMCs the P. orbiculare-reactive TCLs showed a decreased usage of several TCRBVs, although increased usage of certain TCRBVs could be seen in some of the individuals. Further analysis of the CDR3-length polymorphism exhibited a shift in CDR3-length distribution, indicating oligoclonal expansion of T cells specific to different antigens in the P. orbiculare extract. In conclusion we have not found any evidence for superantigen activity in P. orbiculare extract, but our data support the importance of classical major histocompatibility complex (MHC)-restricted allergens in P. orbiculare.

Adolescent↗
PubMed1998

Idiotype immunization combined with granulocyte-macrophage colony-stimulating factor in myeloma patients induced type I, major histocompatibility complex-restricted, CD8- and CD4-specific T-cell responses.

Idiotypic structures expressed on the myeloma Ig protein might be regarded as a tumor-specific antigen. Five patients with IgG myeloma were immunized with the purified serum M-component by repeated intradermal injections together with soluble granulocyte-macrophage colony-stimulating factor (GM-CSF). All patients developed an idiotype (Id)-specific T-cell immunity, defined as blood T cells predominantly secreting interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) (type I cells). Id-specific DNA synthesis was induced in one patient. Delayed-type hypersensitivity against the Id was not evoked. The specific IFN-gamma/IL-2 T-cell response was inhibited (46% to 100%) by a major histocompatibility complex (MHC) class I monoclonal antibody (MoAb) in all five patients. A 5% to 37% inhibition by an MHC class II MoAb was seen in four patients. CD4+ as well as CD8+ T cells enriched by magnetic microbeads contained Id-specific cells. The T cells recognized peptides corresponding to the complementarity-determining regions 1, 2, and 3 of the heavy chain of the Id. There was a transient rise of B cells producing IgM anti-idiotypic antibodies in all patients. The results indicate that immunization of myeloma patients using the autologous M-component and soluble GM-CSF may evoke an Id-specific predominantly MHC class I-restricted type I T-cell response.

Aged↗
PubMed1998

Enhanced prevalence of T cells expressing TCRBV8S2 and TCRBV8S3 in hearts of chronically Trypanosoma cruzi-infected mice.

We have analysed the relative T cell receptor (TCR) BV gene usage in T cells from hearts and spleens of CBA/HJ mice chronically infected with the Tulahuén strain of Trypanosoma cruzi. During chronic infection, CBA/HJ mice recruit T cells at the major site of inflammation (i.e. the heart), with over-representation of certain TCRBV gene subfamilies (TCRBV8S2 and TCRBV8S3). In contrast, no signal or a very weak message from a limited number of T cells was recorded from one heart of the control group. No alteration of TCRBV distribution was recorded in spleens of chronically infected CBA/HJ. Our findings indicate that there is a preferential TCRBV gene usage in the T cell response in the hearts of chronically infected mice. Furthermore, the pattern of CDR3 lengths in inflammatory T cells was altered.

Animals↗
PubMed1997

T cell repertoire in patients with multiple myeloma and monoclonal gammopathy of undetermined significance: clonal CD8+ T cell expansions are found preferentially in patients with a low tumor burden.

The T cell receptor (TCR) variable (V) gene repertoire was analyzed in patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 17), multiple myeloma (MM) stage I (n = 16), MM stages II/III (n = 31) and age-matched controls (n = 27) by immunofluorescence and flow cytometry using a panel of mouse monoclonal antibodies (mAb) (n = 10) against TCR V alpha and V beta gene products. T cell expansion was defined as a value > or = thrice the normal median value for each respective TCR V mAb. Fifty-three percent of all patients displayed CD8+ expansion(s) as compared to 30% of age-matched controls (p < 0.001). Within the CD4 subset, 18% of the patients displayed T cell expansion(s) in comparison to 11% of the controls (not significant). Interestingly, the CD8+ expansion(s) were more frequently noted in patients with a low tumor burden (MGUS/MMI) (73%) as compared to those with advanced disease (MM II/III) (32% and control donors (30%) (p < 0.01). Likewise, multiple CD8+ expansions (two or more) were more common in MGUS/MM I patients than in MM II/III and controls (p < 0.01). The T cell expansions were stable over time in patients with a stable disease. A high degree of clonality of the expansions was detected by TCR CDR3 fragment length analysis, determination of J beta gene usage and nucleotide sequencing. The frequent finding of oligoclonal CD8+ T cell expansions in patients with a low tumor mass, but not in patients with advanced disease justifies further work in order to identify the relevance of expanded CD8+ T cells. In one patient with T cell reactivity against the autologous myeloma idiotype, two expansions within the CD8 population (V beta 3 and V beta 5.2 respectively) displayed no reactivity against the idiotype. Instead, idiotype recognition was confined to a CD8 non-expanded V beta 22+ T cell population, with a highly restricted TCR usage (CDR3 fragment length analysis).

Adult↗
PubMed1997

Peripheral blood T cell expansions in patients with Behcet's disease.

Behçet's disease (BD) is a chronic multisystemic inflammatory disorder characterized mainly by recurrent oral and genital aphthous ulcerations and uveitis. Etiology and pathogenesis of BD remain unknown. T cell receptor (TCR) V alpha/V beta gene product expression as well as Jbeta gene segment expression in peripheral blood of BD patients were analysed to investigate the possible role of T lymphocytes in the etiopathogenesis of BD. Flow cytometry with 12 TCR V-specific MoAbs was used for TCRV analyses. Jbeta gene segment usage by T cell populations expressing certain V betas was determined by polymerase chain reaction (PCR) technique with V beta- and C beta-specific primers, Southern blotting of PCR products, and subsequent hybridization with radiolabelled Jbeta gene segment-specific probes. Although 13 of the 23 BD patients exhibited increases in expression of one or more TCR V-gene products, only expansions among the CD4+ T cell subset were significantly more frequent in BD patients (7/23) compared with healthy controls (0/15) (P = 0.019). Six out of eight cases followed for up to 20 months had at least one expansion correlated with disease activity. A strict preference for particular Jbeta gene segments implicating clonality was apparent in all analysed T cell expansions and correlated well with disease activity. These results suggest a possible involvement of antigen-specific T lymphocytes in the pathogenesis of BD.

Adolescent↗