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M Jeddi-Tehrani

Publications and source records attributed to M Jeddi-Tehrani.

At least 37 records · Page 2Linked to original sources
PubMed1997

T-cell receptor BJ gene segment expression in human umbilical cord blood CD4+ and CD8+ T-cell subsets.

By employing RT-PCR-based technology, followed by Southern-blot analysis, patterns of relative TRC BJ gene segment usage in human CD4+ and CD8+ umbilical cord blood T cells (UCT) from ten children were determined in relation to seven recombined TCR BV gene (sub) families (BV 3, 5S1, 6S1-3, 8, 9, 12 and 18). Normal frequency of usage of individual BJ members was observed to be extremely nonrandom. BJ usage in association with each BV was ranked and mean ranking values were calculated for individual BJs. Moreover, BJ family usage and family ranges as well as individual BJ over-representations were determined. In all these aspects of BJ exon expression, CD4+ and CD8+ UCT displayed similar distribution patterns. Comparisons of BJ usage in UCT subpopulations and in the adult peripheral blood lymphocyte (PBL) counterparts were performed and many similarities were observed. However, discrepancies in two parameters were recorded; contrary to observations in PBL, individual BJ over-representations were virtually absent in UCT, and significantly less wide BJ family ranges were demonstrated in CD8+ UCT relative to CD8+ PBL T cells. These differences support the notion that UCT are in a less dynamic state than are PBL T cells. Hence, despite the fact that PBL T cells are subjected to continuous antigenic challenge, the striking resemblance of PBL and UCT with regard to the overall individual relative usage, ranking, mean ranking and family utilisation of BJ gene segments, irrespective of the choice of recombined BV exons, may suggest a relatively nondiscriminatory role for the BJ gene product in antigen recognition as compared to those encoded by the BV, (N) and BD gene segments.

Blotting, Southern↗
PubMed1996

Enhanced prevalence of T cell receptor V beta 7 gene family expression in human intestine-associated T lymphocytes.

Relative levels of expression of T cell receptor variable (V) beta and joining (J) beta gene segments were determined in T cells derived from intestinal biopsies of healthy mucosal areas, mesenteric lymph nodes and peripheral blood of the same individuals. Samples taken from patients suffering from inflammatory (n = 8) and non-inflammatory (n = 8) bowel diseases were analyzed by semi-quantitative polymerase chain reaction-based methods. In the intestine, fewer (median = 3.5) V beta gene segments constituted more than 50% of the T cell receptor V beta repertoire compared to that of peripheral blood T cells (median = 7, P < 0.001). Interestingly, in all sixteen individuals studied, intestinal T lymphocytes (IL-T) expressed the V beta 7 gene family to a higher degree than did T cells in the paired peripheral blood and mesenteric lymph nodes (P < 0.001). T cell receptor J beta gene segment analyses of V beta 7+ T cells revealed no significant difference in oligoclonality rates between peripheral blood (4/16) and intestine (7/16) (P = 0.46). Hence, overexpression of intestinal TCR V beta 7 message does not seem to be due to oligoclonal expansions in the majority of the samples.

Adolescent↗
PubMed1996

RT-PCR based analysis of T-cell receptor B variable region gene usage in normal human breast skin resident T lymphocytes (SRT).

The skin interfaces directly with the external environment that contains innumerable infectious agents. Therefore, an appropriate and rapid immunologic response is required to preserve internal homeostasis. An essential feature of the "skin immuno system' (SIS) is the presence of substantial numbers of T cells in normal skin. The T-cell receptor repertoire from normal human breast skin was analysed quantitatively and qualitatively by using PCR amplification of reverse transcribed RNA, T-cell receptor BV3 and BV14 gene usage was increased in skir T lymphocytes in all individuals tested (n = 8) compared to peripheral blood CD4+ and CD8+ T lymphocytes from the same individuals. The T-cell receptor junctional diversity analysed by high resolution gel electrophoresis showed skin T-cell BV3 and BV14 gene usage to be predominantly polyclonal. Superantigen stimulation of T cells in human skin is considered a likely explanation of the present finding.

Breast↗
PubMed1996

Overexpression of select T cell receptor V beta gene families within CD4+ and CD8+ T cell subsets of myasthenia gravis patients: a role for superantigen(s)?

BACKGROUND: The principal symptoms of myasthenia gravis (MG), muscle weakness and fatigue due to impaired neuromuscular transmission, are caused by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). The mechanisms underlying the autoimmune response, however, appear to be initiated by activation of specific HLA class II-restricted CD4+ T lymphocytes. Thus, central to elucidating the causation of MG is determining how T cells are recruited to contribute to misguided immunological assaults on the major autoantigenic target, AChR. MATERIALS AND METHODS: By combining a polymerase chain reaction (PCR)-based strategy and Southern blot technique, we have analyzed the frequency of expression of 22 individual T cell receptor (TCR) V beta gene subfamilies in CD4+ and CD8+ peripheral blood T cell subsets derived from eight MG patients and seven healthy controls. The quantification of relative usage of individual TCR J beta gene segments was performed by hybridization of PCR-amplified products (specifically V beta 1-C beta) with a complete panel of 32P-5'-end-labeled J beta-specific oligonucleotide probes, followed by scanning analysis of autoradiographs. RESULTS: Comparisons of data obtained from V beta analyses of T cells from MG patients with those from healthy individuals established that MG patients significantly overexpressed V beta 1, V beta 13.2, V beta 17, and V beta 20 gene family members within both CD4+ and CD8+ T cell subpopulations. Moreover, analysis of the relative utilization of individual TCR J beta gene segments in V beta 1+/CD4+ and V beta 1+/CD8+ T lymphocytes revealed distribution patterns in patients indistinguishable from those recorded in the corresponding cell subsets derived from controls. CONCLUSIONS: T lymphocytes from MG patients displayed a biased overexpression of four TCR V beta gene segments: V beta 1, V beta 13.2, V beta 17, and V beta 20. The relative frequencies of association of individual V beta 1 (D beta) J beta combinations revealed that J beta gene usage in the V beta 1-over-represented T cell subsets had normal distribution patterns. It can thus be deduced that J beta gene segment products appear not to have a selective effect on the process leading to overexpression of V beta 1 exons in MG patients. Hence, our observations suggest a possible role for superantigen(s) in the T cell activation in MG patients.

Adult↗
PubMed1995

T-cell receptor J beta gene segment usage in immature and mature human thymocytes.

Immature double positive (DP, CD4+CD8+) and mature single positive (SP, CD4+CD8- and CD4-CD8+) human thymocytes from nine thymi were analysed for their complete patterns of relative TCR J beta multigene member usage in relation to six rearranged V beta family exons (V beta 5.1, 6.1-3, 8, 9, 12 and 18). Each sample tested contained mRNA transcripts corresponding to all potential V beta(D beta)J beta combinations. Individual J beta gene segments were expressed in a similar, highly non-random manner both in SP and DP thymocytes, irrespective of original genomic position of the individual associated V beta exon. In addition, ranges of family usage and frequency of individual over-representations of J beta gene segments, as determined in DP and SP thymocyte populations, displayed no significant differences. Upon comparison of DP and SP thymocytes, however, a discrepancy in one aspect of J beta gene utilization was established: decreasing J beta family 1/J beta family 2 ratios were determined to be positively correlated with increasing maturity of thymocytes, a condition further supported by data previously obtained from studies of PBL T cells. At the individual J beta gene level, the observed gradual modification of the relative family usage can largely be explained by a significant shift from a higher J beta 1.1/J beta 2.7 ratio in DP to a higher J beta 2.7/J beta 1.1 ratio in SP thymocytes. Altogether, the present results imply that selectional processes in the thymus appear to have only minor consequences on the distribution pattern of expressed J beta exons. Hence, the disproportionate pattern of TCR J beta gene usage seems to be established mainly at the recombinatorial level followed by minor adjustments during thymic and post-thymic events.

Cell Differentiation↗
PubMed1994

Nonrandom T-cell receptor J beta usage pattern in human CD4+ and CD8+ peripheral T cells.

Association frequencies of TCR J beta gene segments with six V beta families (V beta 3, 6.1-3, 8, 9, 12, and 18) were analyzed in T-cell populations obtained from healthy blood donors. The six selected V beta families are located at various chromosomal positions relative to other recombinatorial elements (D beta, J beta, C beta). We report here that in CD4+ as well as CD8+ T-cell subsets, all 13 J beta gene segments were used in combination with all the V beta s tested and that no correlation between the genomic position of the individual V beta s and J beta gene segment usage was observed. J beta gene segment usage was found to be nonrandom in general, with J beta 2.7 and J beta 2.4 exhibiting highest and lowest frequency of utilization, respectively. J beta family 2 was used more frequently than J beta family 1 by the two T-cell subsets. Some individual J beta gene segments were skewed toward either CD4+ or CD8+ T cells. Thus, J beta 1.3 and J beta 1.6 were consistently biased toward expression in CD4+ T cells. In contrast, when combined with V beta 8 or V beta 9, J beta 2.1 results were skewed dramatically toward expression in CD8+ T cells. We also found 70 cases of expanded individual V beta/J beta associations in a total of 1092 investigated combinations, 62 of which were confined to the CD8+ T-cell populations. CD8+ T-cell populations are thus much more likely to contain TCR V beta/J beta-restricted expansions than CD4+ T cells.

Blotting, Southern↗
PubMed1993

Restricted T cell receptor V-beta and J-beta usage in T cells from interleukin-2-cultured lymphocytes of ovarian and renal carcinomas.

Tumour-infiltrating lymphocytes (TIL) are often observed in human tumours and their presence has been correlated with a better prognosis. It has been suggested that TIL are enriched for tumour-specific cytotoxic cells, and TIL activated and expanded in vitro by interleukin-2 (IL-2) are currently used in the therapy of human cancer. We have studied the T cell repertoire in IL-2-expanded TIL cells from patients with ovarian and renal carcinoma using T-cell-receptor-V-beta-specific monoclonal antibodies and a polymerase-chain-reaction-based Southern blot technique for analysis of J-beta usage. In TIL lines derived from three of nine patients with ovarian carcinomas and from two of eight patients with renal carcinomas, selective usage of the V-beta 6 or V-beta 5 T-cell receptor gene products was found. The majority of the cells were CD4+, with up to 40% of the T cells utilizing the same V-beta gene. T-cell lines derived from peripheral blood lymphocytes from patients or healthy donors contained normal levels of V-beta subsets. Only moderate levels of V-beta 6+ T cells were detected from freshly isolated TIL and the increase of this subpopulation appeared as a result of in vitro culture. The level of clonal restriction, as measured by the usage of J-beta gene segments within the V-beta 5 or V-beta 6 families, was analysed using a recently developed technique based on the polymerase chain reaction. Evidence for restricted J-beta usage was detected only in TIL expanded in vitro, while this was not the case in freshly isolated tumour-derived lymphocytes or T cell lines obtained from peripheral blood lymphocytes. The presence of a population with biased T cell receptor expression in cells derived from tumour tissue could be explained by their activation in vivo as a result of contact with tumour antigens and should be taken into consideration when discussing the therapeutic efficiency of IL-2-expanded TIL.

Antibodies, Monoclonal↗
PubMed1993

HIV infection leads to differential expression of T-cell receptor V beta genes in CD4+ and CD8+ T cells.

OBJECTIVE: To analyse variation in T-cell receptor (TCR) V beta gene expression in T cells in HIV-infected individuals. DESIGN: Because there are very few monoclonal antibodies available for studying TCR V beta gene expression, we used polymerase chain reaction (PCR) to analyse the TCR V beta repertoire in HIV-infected individuals using specific primers for 20 distinct families of TCR V beta. METHODS: Evaluation of TCR V beta gene expression in peripheral blood from HIV-1-infected individuals [two in Centers for Disease Control (CDC) stage II, five in CDC stage III and four in CDC stage IV]. Complementary DNA was produced from CD4+ and CD8+ T cells, amplified by PCR and analysed after Southern blotting and hybridization with a C beta-specific oligonucleotide probe. RESULTS: V beta gene expression was dramatically modified, especially in AIDS patients. The CD4+ T-cell subset showed both overexpression (V beta 2) and deletions or underexpression (V beta 9-V beta 20), whereas these gene segments were expressed normally in the CD8+ subset. Only V beta 3 was deleted or underexpression in both CD4+ and CD8+ populations in AIDS patients. CONCLUSIONS: HIV-1 infection induces CD4+ T-cell deficiency, both in total numbers and by causing a paucity of select V beta gene expression in this subset. In addition, the V beta 3 gene family was deleted or underexpressed was observed in both CD4+ and CD8+ T-cell subsets from patients in CDC stage IV. These results are compatible with changes in V beta gene expression known to occur under the action of endogenous or exogenous superantigens.

Base Sequence↗
PubMed1992

Potentiation of transmembrane signaling by cross-linking of antibodies against the beta chain of the T cell antigen receptor of JURKAT T cells.

Three monoclonal antibodies (mAb) 2D1, 3B9, and 3B12 were produced by immunizing BALB/c mice with JURKAT cells. These mAb induce comodulation of the TCR/CD3 complex expressed on JURKAT cells, but do not react with the CD3- JURKAT variant, J.RT3.T3.1. Immunoprecipitation studies with detergent-solubilized JURKAT cell lystes indicate that these mAb react with proteins having characteristics of the TCR molecules. Their low reactivity with peripheral blood mononuclear cells (PBMC) and lack of reactivity with other CD3+ T cell lines suggest that they may be anti-idiotypic mAb. Results from binding inhibition assays, reactivity with PBMC, and generation of transmembrane signals suggest that these three anti-TCR mAb recognized different epitopes on the TCR beta chain of JURKAT cells. Although the three mAb are capable of inducing the production of inositol phosphates and cytosolic free Ca2+ increase in JURKAT cells, their stimulatory capacities vary and are lower than that observed by anti-CD3 antibody (OKT3) stimulation. However, crosslinking these mAb with rabbit antimouse immunoglobulins potentiates the stimulatory response to comparable levels induced by OKT3. These mAb could be useful as tools to study V beta 8+ T cells in relation to antigen-specific activation.

Animals↗
PubMed1992

Characterization of the colorectal antigen IOR-C2.

A colorectal antigen (IOR-C2) was characterized by a monoclonal antibody produced against the colon cancer cell line SW1116. By immunohistochemical staining the antigen was abundant and strongly expressed in epithelium of normal colon whereas colorectal carcinomas showed a more variable and heterogenous reactivity to the antibody (IOR-C2). Radioimmunoprecipitates of SW1116 cell homogenates showed a 160-200 kD band in SDS gels. Physicochemical characterization indicate that at least two IOR-C2 reactive sites are present on the antigen tested and that it is mainly an 0-linked glycoprotein carbohydrate chain which can also be N-linked to the protein. The expression of IOR-C2 mimics that of the colon associated antigen (CAA) and NCC-CO-450 antigen but is distinct from these with regard to its expression in carcinomas as well as its physicochemical characteristics.

Animals↗
PubMed1992

Analysis of J beta gene segment usage by CD4+ and CD8+ human peripheral blood T lymphocytes.

Certain T cell antigen receptor V gene products in man have been shown by us and others to display a reproducible bias for preferential expression in CD4+ or CD8+ T cell subsets. In order to investigate whether such a skewed representation of V gene segments is also present at the J gene segment level, we tested the relative J beta gene usage by V beta 5.1 + T cells, as this V beta gene is biased towards CD4+ T cell expression in virtually all individuals. To analyze the usage of the 13 J beta gene segments, we developed a new approach using V beta 5.1 and C beta specific oligonucleotides as 5' and 3' primers respectively for polymerase chain reaction (PCR) amplification of cDNA derived from CD4+ or CD8+ peripheral blood lymphocyte (PBL) T cells. The PCR products were visualized for reactivity with individual J beta 1.1-1.6 and J beta 2.1-2.7 32P-labelled oligonucleotide probes using autoradiography and quantitative gel-scanning. Eleven normal blood donors provided the PBL T cells. The results showed that in every individual's V beta 5.1+ T cell populations (CD4 and CD8), all V beta/J beta combinations were used although at varying but reproducible levels for each J beta gene. Thus, no discernible disallowance of combinations existed. Moreover, we could show that six of 13 J beta genes were unequally expressed when compared in pairs with regard to expression in CD4+ and CD8+ T cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Monoclonal antibodies to Lepidoglyphus destructor: delineation of crossreactivity between storage mites and house dust mites.

We have developed monoclonal antibodies (MoAbs) to the storage mite Lepidoglyphus destructor (Ld). Employing these anti-Ld MoAbs Ld-MoAbs) in ELISA and ELISA inhibition techniques we have analysed the reaction pattern of Ld-MoAbs to both non-pyroglyphid and pyroglyphid mites. The storage mite Glycyphagus domesticus (Gd) exhibited most efficient inhibition, followed by Acarus siro (As), Tyrophagus putrescentiae (Tp), Dermatophagoides pteronyssinus (Dpt) and Euroglyphus maynei (Em). Of the two pyroglyphid species, Dpt showed at least 1000 times less inhibition than Gd. Two of the MoAbs immunoprecipitated a band of 39 kD whereas the third reacted weakly, with a high-molecular band of approximately 110 kD. The Ld extract was also subjected to various reagents and conditions and the antigen was heat stable, it was not affected by low pH, or sensitive to dimethyl sulphoxide (DMSO) or paraformaldehyde. After exposure of the extract to various reagents, such as protease trypsin and periodate, we conclude that the epitopes recognized by Ld-MoAbs were of carbohydrate rather than of protein nature. It would thus seem that MoAbs recognize the carbohydrate part of a glycoprotein.

Animals↗
PubMed1992

A persistent T cell expansion in the peripheral blood of a normal adult male: a new clinical entity?

A dramatic and persistent T cell expansion in a healthy adult male was initially identified, using anti-T cell receptor for antigen (TCR)-specific MoAbs. The expanded T cells were found to be expressing TCR containing V alpha 12.1 and V beta 5.2, and they composed approximately one third of all the CD8+ T cells. The cells were shown to be not only non-activated (HLA-DR-, IL-2R-) but also of 'virgin' cell type (CD45RA+/CD45RO-) and they persisted over the observation period of more than one and a half years. Various T and B cell markers, and all other laboratory and physical parameters analysed, were normal. The expanded CD8+ T cells were further characterized by polymerase chain reaction (PCR) amplification, using V beta- and C beta-specific primers, followed by hybridization with J beta-specific probes. Close to 90% of the V alpha 12.1+ V beta 5.2+ T cells were found to utilize the J beta 2.5 gene segment, thus strongly suggesting the expanded T cells to be monoclonal. The condition may constitute a T cell counterpart to 'monoclonal gammopathy of undetermined significance' (MGUS), and by analogy we suggest it should be designated 'monoclonal T cell expansion of undetermined significance' (MTUS).

Adult↗
PubMed1992

Clostridium difficile toxin A induces multinucleation in the human leukemic T cell line JURKAT.

Clostridium difficile toxin A is a cytotoxic enterotoxin known to be active on all mammalian cell lines tested up to now. It induces a disruption of the cytoskeleton, particularly the microfilament system, leading to inhibition of cell proliferation. Here, we describe some effects of toxin A on the leukemic T cell line JURKAT. Cells exposed to the toxin did not divide, as cell numbers remained constant for 3 days in the presence of 0.5 to 1.0 micrograms/ml of the toxin. However, these cells were found to become multinucleated, a phenomenon which was time- and dose-dependent. After treatment for 72 h with 0.5 micrograms/ml toxin A, 95% of the cells were multinucleated and had a considerably increased cell diameter. These effects in JURKAT cells were partially reversible upon removal of the toxin within 12 h after the beginning of toxin exposure, but irreversible after 24 h of toxin treatment. These results suggest a continuing nuclear division in the absence of cytoplasmic division, i.e., an effect of toxin A on contractile ring formation. The JURKAT cell is the first cell type reported to respond to toxin A with multinucleation.

Bacterial Toxins↗
PubMed1991

Identification of a new major allergen of 39 kilodaltons of the storage mite Lepidoglyphus destructor.

The allergen composition of a non-denatured extract of the storage mite Lepidoglyphus destructor was studied by a combination of hybridoma technology, sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and a sandwich radio-allergosorbent test (four-step RAST). Using hybridoma technology, monoclonal antibodies (mAbs) were generated against the non denatured extract of the L. destructor. After screening by ELISA, mAb 42B6 was selected for further studies. This mAb specifically recognized an antigen of L. destructor of 39 kDa in SDS-PAGE. By a sandwich RAST, sera from 8 patients with known allergy to L. destructor were compared with control sera from 8 allergic patients. The results showed the presence of specific IgE against the 39-kDa protein in the sera of the test group, but not in the control group. There was also a good correlation observed between these data and the results obtained with the classical RAST. These results indicate that the newly identified antigen of 39 kDa is a major allergen of the storage mite Lepidoglyphus destructor.

Allergens↗