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T Hercend

Publications and source records attributed to T Hercend.

At least 91 records · Page 5Linked to original sources
PubMed1988

A unique V-J-C-rearranged gene encodes a gamma protein expressed on the majority of CD3+ T cell receptor-alpha/beta- circulating lymphocytes.

We have recently described an mAb, anti-Ti gamma A, that recognizes an antigenic determinant carried by a TCR gamma chain. This antibody binds to approximately 3% of human PBLs and delineates a CD2+, CD3+, TCR-alpha/beta-, CD4-, CD8+/-, CD5+, NKH1-, and HLA class II- subset. The present study was designed to identify the gene encoding the Ti gamma A epitope. A first analysis was carried out on a previously characterized TCR gamma + fetal-cloned cell line termed F6C7. It was found that F6C7 cells have one gamma rearrangement on each chromosome: one joins V gamma 3 to J gamma 1, and the second joins V gamma 9 to J gamma P. Because only the latter allele appeared to be transcribed in the F6C7 lymphocytes, these data strongly suggested that anti-Ti gamma A mAb is specific for either a V gamma 9 or a V gamma 9-J gamma P-encoded peptide. To confirm this point, we studied an additional series of 13 randomly selected Ti gamma A+ cloned cells derived from peripheral blood of three distinct adult individuals. Each one of these lymphocytes was shown to both possess and transcribe a V gamma 9-J gamma P-C gamma 1-rearranged gene. It is therefore concluded that a predominant subpopulation of CD3+ TCR-alpha/beta- human circulating T lymphocytes (namely, the subset defined by anti-Ti gamma A mAb) surface expresses a gamma protein with a limited potential of variability from one cell to another.

Adult↗
PubMed1988

Evidence for expression of two distinct T cell receptor beta-chain transcripts in a human diphtheria toxoid-specific T cell clone.

We have cloned and sequenced the human T cell receptor alpha- and beta-chains cDNA present in a lambda gt10 library derived from a human CD4+ diphtheria toxoid-specific T cell clone, PH28. Two 1.3-kb beta-transcripts within frame V, D, J joining were found. These two functional beta-transcripts use two members of different V beta-families, V beta 3 and V beta 4, one joined to D beta 1-1, J beta 1-1, C beta 1, the other joined to D beta 1-1, J beta 2-1, C beta 2. Moreover, we have cloned the two different V beta germ-line counterparts whose sequences confirm that these two V beta are not pseudogenes. Analysis of T cell receptor beta and alpha rearrangements in PH28 showed that a single rearrangement on each chromosome could be assigned either at the J beta or the J gamma loci. These results strongly suggest an absence of allelic exclusion for 1.3-kb mRNA beta-transcripts in a human antigen-specific T cell clone.

Amino Acid Sequence↗
PubMed1988

Further evidence for a sequentially ordered activation of T cell rearranging gamma genes during T lymphocyte differentiation.

Recently, we have shown that the majority of human peripheral lymphocytes with a T cell receptor (TcR) gamma/delta receptor use a unique gamma chain recognized by the anti-TigammaA monoclonal antibody. This predominantly expressed gamma protein is encoded by a rearranged gene where the V9 segment has joined the JP segment located upstream of the C gamma 1 region (TRGC1). Peripheral TigammaA+ cells were further studied here to shed light on the relation between the two types of TRG rearrangements namely those involving the first (TRG1) vs. the second (TRG2) J-C region. Thirteen clones reactive with anti-TigammaA were tested; it was found that the second TRG allele (i.e., the one which does not involve V9-JP) of these cells was either in germ-line configuration or, more frequently, rearranged with a downstream V gamma gene joined to a J segment of the TRG1 region. These data suggest that productive rearrangements on TRG1 leading to the production of a surface-expressed gamma chain occur before rearrangements involving the TRG2 region. It supports the view that TRG genes are subjected to a sequentially ordered activation during the process of T lymphocyte differentiation.

Cell Differentiation↗
PubMed1988

Triggering of the phosphoinositide transduction pathway by a monoclonal antibody specific for the human gamma/delta T cell receptor.

We have developed a monoclonal antibody (mAb), termed anti-TigammaA, which recognizes an antigenic determinant carried by a variable segment of the T cell receptor (TcR) gamma chain. This determinant, encoded by the V gamma 9 gene, is expressed on approximately 3% of peripheral blood lymphocytes. In the present study, we have found that binding of anti-TigammaA mAb to its specific ligand results in the triggering of the phosphatidylinositol (PI) cycle-related metabolic process. Indeed, an increased labeling of both phosphatidic acid and PI, related to an enhanced turnover of PI cycle-dependent phospholipids, was observed following exposure of 32P orthophosphoric acid-labeled cells to anti-TigammaA mAb. In addition, there was a rapid rise in intracellular free calcium concentrations. Similar experiments have been performed previously on CD3+ TcR alpha/beta- -cells with an anti-CD3 mAB. They predicted that signals produced by the interaction between the second TcR and its ligand(s) would be transmitted via the PI cycle-linked intracellular second messengers. We confirm this hypothesis in an experimental system where stimulation occurs directly through the gamma/delta receptor structure.

Antibodies, Monoclonal↗
PubMed1988

Clonal analysis of human T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis.

Human T lymphocytes infiltrating the liver in chronic active hepatitis B (CAH-B) and primary biliary cirrhosis were isolated from liver biopsy cores, cloned by limiting dilution technique and expanded in vitro. Phenotypic and functional analysis demonstrates that this tissue infiltrate represents a heterogeneous cell population. However, when compared to peripheral blood lymphocytes of the same patients, a marked enrichment for T8+ cytotoxic T cells was found to exist at a local site in both types of chronic liver disease. These data provide support for the notion that liver cell injury in CAH-B and PBC may be mediated by a common immunologic mechanism likely executed by cells of the T lineage.

Antibodies, Monoclonal↗
PubMed1988

Cloned CD3+ TcR alpha/beta- Ti gamma A- peripheral blood lymphocytes compared to the Ti gamma A+ counterparts: structural differences of the gamma/delta receptor and functional heterogeneity.

We have assessed the organization of T cell gamma rearranging genes (TRG) in circulating TcR gamma/delta+ lymphocytes which do not express V gamma 9-encoded Ti gamma A+ gamma chain. Following purification of the minor TcR gamma/delta+ Ti gamma A- fraction, cloned cell lines were developed from peripheral blood of 5 individuals. Out of the 26 clones studied, only 3 TcR gamma/delta+ Ti gamma A- cells were found to express a disulfide-linked C1-encoded gamma chain. The remaining 23 Ti gamma A- clones with a C2-encoded nondisulfide-linked receptor were found to display rearrangements of various V genes to J2 segments on both chromosomes; there was no predominance of a unique rearrangement even though the TRG-V3 and -V4 genes belonging to subgroup I were frequently employed. Together, these findings further strengthen the hypothesis that lymphocytes with a C gamma 1 encoded chain are produced earlier in T cell ontogeny than the C gamma 2 counterparts. The "non-major histocompatibility complex (MHC) requiring" (i.e., "natural killer-like") cytotoxicity mediated by many TcR gamma/delta+ Ti gamma A- cells appeared to be very low as compared to that of Ti gamma A+ clones. Yet, treatment by the OKT3 monoclonal antibody revealed a strong lytic potential in the Ti gamma A- lymphocytes with little, if any, natural killer-like activity. Thus, with respect to the latter function, a substantial heterogeneity is found in cells expressing distinct gamma chains. In an attempt to characterize undefined specificities of Ti gamma A- lymphocytes, they were screened against a panel of Epstein-Barr virus-transformed B cell lines homozygous for HLA-DR1 to DR10 determinants; one of the clones was found to recognize DR7. In light of reports from other groups describing class I-related specificities, it is apparent that TcR gamma/delta+ lymphocytes are able, like the TcR alpha/beta+, to recognize and kill target cells through either an MHC-dependent (with involvement of either class I or class II gene products) or a non-MHC-requiring pathway.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

A novel human V delta gene expressed predominantly in the Ti gamma A fraction of gamma/delta+ peripheral lymphocytes.

We have characterized a functional T cell receptor (TcR) delta transcript in a Ti gamma A+ human cloned cell line derived from peripheral blood. This cDNA includes a novel V gene (V-AB12), whose expression was initially studied in a series of TcR gamma/delta+ clones. Nine Ti gamma A+ clones derived independently from distinct donors have been tested: each of them was found to possess a unique V-AB12/J-IDP2 5.5-kb Eco RI rearrangement, which was constantly transcribed. Surface expression of the protein encoded by this unique rearranged gene was demonstrated by immunoprecipitations performed on three Ti gamma A+ polyclonal cell lines using a specific rabbit heteroantiserum. Further analysis strongly suggested that a monoclonal antibody (mAb), designated anti-BB3, detects a V-AB12-encoded antigenic determinant on the cell surface. Double-color immunofluorescence analysis of peripheral blood lymphocytes from ten donors indicated that most BB3+ cells are recognized by anti-Ti gamma A mAb. In previous studies, we have shown that a majority of TcR gamma/delta+ peripheral T cells expresses a gamma chain including V9 (Ti gamma A) and most frequently JP-encoded peptides. Given the present results on the delta chain, it can be concluded that, in many individuals, a predominant fraction (V gamma 9+/V-AB12+) of circulating CD3+ TcR alpha/beta- T lymphocytes expresses a receptor with little, if any, combinatorial diversity.

Amino Acid Sequence↗
PubMed1988

T cells expressing gamma delta chain receptors in rheumatoid arthritis.

Whereas the majority of T cells use alpha and beta chains to form their T-cell receptor, a small minority of T cells, which do not express the CD4 or CD8 surface markers, use other chains termed gamma and delta to form their receptor. Flow cytometry was performed on cells isolated from the blood and synovial joints of patients with rheumatoid arthritis. Monoclonals which recognise the gamma and delta chains were used to compare the proportion of TCR gamma delta cells in these sites. Approximately half the patients had more TCR gamma delta in the joints than in their blood and one newly diagnosed patient had high numbers of TCR gamma delta cells in both blood and joints. In this preliminary study it is not possible to evaluate the role of these cells in the disease process, but it is of interest that in some RA patients there is an overabundance of both T cells that arise early in ontogeny (TCR gamma delta cells) and B cells that arise early in ontogeny, the CD5 B cell.

Antibodies, Monoclonal↗
PubMed1988

Characterization of functional surface structures on human natural killer cells.

Recent studies on human NK cells have identified a number of surface antigens that can be utilized to define this population of cells and to identify functionally distinct subsets within this heterogeneous population. In addition, it has been possible to associate specific functional activities with several antigens expressed on NK cells as well as other hematopoietic cells. This information, which is summarized in Table III can be utilized to develop a framework for the classification of cytolytic effector cells. Of primary importance, this classification identifies subsets of cytolytic cells with distinct functional repertoires and distinct cytolytic mechanisms. The majority of NK cells in unstimulated peripheral blood and the majority of NK clones express NKH1 and CD2 antigens but do not express CD3 antigen. These cells morphologically appear as large granular lymphocytes and have broad cytolytic activity against a variety of allogeneic targets without primary sensitization. Consistent with the finding that these cells are CD3 negative, they have not been found to have rearrangement of genes encoding for TCR, or functional mRNA transcripts of either TCR alpha, TCR beta, or TCR gamma genes. In addition, these cells do not express heterodimeric surface proteins similar to those that have now been demonstrated to be MHC-restricted T cell receptors for antigen. Taken together, these findings provide strong evidence that NKH1+CD3- NK clones do not interact with target cells through a T cell receptor-like structure. Nevertheless, these NK cells do share several properties with conventional CTL. These functional T cell characteristics include (1) expression of CD2-T11/E rosette receptor antigen, and (2) utilization of LFA-1 surface antigen to enhance effector cell adhesion to target cells. As previously demonstrated for T cells, NK cells can be activated through the CD2 molecule and this has recently been shown to result in the enhancement of cytolytic function by these effectors. Since CD2 can also function as a cell surface ligand for LFA-3, an antigen expressed on NK targets, the CD2 molecule may be considered as a potential NK receptor structure. The fact that a very small subset of NK cells (approximately equal to 10%) as well as some NK clones (JT11) does not express CD2 argues against a potential role for CD2 as the NK cell receptor. Certainly, further studies will be necessary to clarify the role of CD2 on NK cells and to identify the mechanisms whereby NKH1+CD3- NK cells interact with targets in a non-MHC-restricted fashion.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1988

Prominent expansion of circulating lymphocytes bearing gamma T-cell receptors, with preferential expression of variable gamma genes after allogeneic bone marrow transplantation.

The presence of two distinct T-cell receptors (TCR) alpha/beta dimers or gamma/delta dimers, was systematically analyzed in peripheral blood lymphocytes form 26 recipients of allogeneic bone marrow transplants for leukemia. When using monoclonal antibody WT31, which recognizes a common epitope on the alpha/beta heterodimer, the expansion of peripheral CD3+, WT31- cells to 40% of the PBLSs was detected in two patients. In patient 2, the presence of circulating TCR gamma-bearing cells was directly demonstrated with monoclonal antibody Ti gamma A directed against the V gamma 9 J gamma p gene products. From CD3, WT31- clones derived from patients 1 and 2, sequential immunoprecipitations were performed with anti-CD3 and anti-C gamma to determine the CD3-associated structure. Molecular weights of gamma subunits were different in both patients, thus indicating structural heterogeneity. The ability of TCR gamma clones to proliferate when stimulated with anti-CD3 beads was observed for clones from patient 2, whereas this response required exogenous interleukin-2 for clones from patient 1. We have already shown that the TCR gamma cells from patient 1 might have played a role in the immunodeficient state. Similar conclusions cannot be drawn from patient 2. Southern blot analysis of total PBL gamma cell lines and clones indicated that this major circulating subset of TCR gamma cells retained a TCR beta gene in germline configuration and preferentially expressed a single V gamma gene, V gamma 5 for patient 1 and V gamma 9 for patient 2.

Antibodies, Monoclonal↗
PubMed1988

[Principles of treatment with cells called "LAK" cells].

A novel approach for immunotherapy of cancer is presently under investigation. This treatment initially developed by Steven Rosenberg and colleagues is based on both the transfusion of autologous lymphocytes preactivated in vitro using interleukin 2 and the simultaneous infusion of the lymphokine in vivo. The two major limiting factors for these new protocols are, on the one hand, the heavy infrastructure necessary for in vitro cell treatment, and, on the other hand, the dose-dependent toxicity of IL2 infusions. Results of clinical trials are still preliminary; they suggest that the therapy may be of interest in melanomas and renal cell carcinomas. However, only a minority of patients with these relatively susceptible tumors display substantial responses. Thus, the protocols need to be improved which makes it critical to understand the biological mechanisms underlying tumor regression in vivo. The dominant working hypothesis is that IL2 enhances firstly in vitro and then in vivo the activity of certain lymphocytes able to destroy tumor cells via a direct cytotoxic effect. This view supported by murine experimental models remains to be demonstrated in the human. One way of testing it, is to infuse highly purified fractions of killer lymphocytes instead of the whole peripheral blood suspensions that are used presently. We are attempting to develop this approach and a trial is presently beginning at the Gustave-Roussy Institute in a series of patients with renal cell carcinoma.

Humans↗
PubMed1987

A novel subset of human lymphocytes with a T cell receptor-gamma complex.

We have previously characterized a CD3+ T cell receptor (TCR) alpha/beta- human fetal cloned cell line, termed F6C7, which surface-expresses a CD3-associated gamma chain identified by anti-NKFi, an mAb with a restricted clonotypic reactivity. Here, we have produced an additional antibody, anti-Ti-gamma A, which recognizes a public epitope of the gamma molecule defined by anti-NKFi. Ti-gamma A is present on approximately 3% of circulating lymphocytes with a wide range (1-15%) among 30 healthy individuals tested. Two-color immunofluorescence experiments performed with anti-Ti-gamma A and BMA 031 mAb (a reagent specific for the TCR-alpha/beta receptor) showed that surface expression of Ti-alpha/beta and Ti-gamma A is mutually exclusive. Moreover, it was found that most Ti-gamma A+ cells are CD2+, CD3+, CD4-, CD5+, NKH1-, HLA class II-negative. In contrast, the expression of the CD8 molecule on these T lymphocytes appears to be variable from one individual to another. Finally, we found that Ti-gamma A+ cells represent a majority of peripheral lymphocytes that express CD3 proteins but not the TCR-alpha/beta heterodimer. The delineation of this unique lymphocyte subset should help further studies on the biology of cells with a CD3-associated gamma complex.

Animals↗
PubMed1987

rIL 2-induced proliferation of human circulating NK cells and T lymphocytes: synergistic effects of IL 1 and IL 2.

Cells participating in the rIL 2-induced proliferation of resting PBMC were identified by using different methods of cell purification. NK cells recovered in the light density fraction of Percoll gradients responded, as already known, directly to rIL 2 by strong proliferation. In contrast, large T lymphocytes co-purifying with NK cells, and small T cells sedimenting in the high density area of the Percoll gradients, were virtually unresponsive when cultivated in the sole presence of rIL 2. However, the addition of either irradiated autologous monocytes or highly purified IL 1 allowed both kinds of T cells to undergo cell division. Stringent elimination of possibly contaminating NK cells (NKH-1+) and/or activated T cells (TNKTAR, Tac+, HLA-DR+) from the high density T cells by complement lysis did not impair rIL 2-induced cell proliferation, indicating entire responsiveness of these cells to the synergistic action of IL 1 plus IL 2. Both high density CD4+ and CD8+ participated in this phenomenon, with an apparent advantage for CD4+ cells. All Tac+ cells emerging in a 6-day culture of these cells expressed the WT31 antigen, which indicates that T cells involved in rIL 2-induced proliferation are conventional mature T cells. The relative precursor frequencies of NK cells, large T lymphocytes, and small T lymphocytes that proliferated in response to rIL 2 were analyzed by limiting dilution analysis. The frequencies of clonal growth of NK cells and low density T lymphocytes were approximately the same (1/103 vs 1/185), whereas that of high density T cells was four times lower (1/458). Thus, we clearly demonstrate that resting T cells, defined as such by morphological, density, and phenotypic criteria, are able to proliferate in response to IL 2 in the presence of IL 1 without antigenic or mitogenic triggering.

Cytotoxicity, Immunologic↗
PubMed1987

A T chronic lymphocytic leukemia with large granular lymphocytes. Phenotype and functions of leukemic cells under in vitro treatment by differentiation inducers.

We reported the morphologic, phenotypic and functional characteristics of leukemic cells with natural killer (NK) properties in a case of T chronic lymphocytic leukemia with large granular lymphocytes. These cells were cytologically and cytochemically characterized as phosphatase acid positive large granular lymphocytes (LGL), and presented parallel tubular arrays at the ultra structural level. They displayed a CD2, CD3, CD8, CD11, Leu 7, and Leu 11 positive phenotype while they lacked B cell markers including surface immunoglobulins. In addition, they expressed human leukocyte antigens (HLA) Class I, but no Class II antigens. These phenotypic studies were also performed after cells were cultured in vitro with 12-0-tetradecanoyl phorbol 13-acetate, gamma interferon, 5-azacytidine, sodium butyrate, phytohemagglutinin, and interleukin 2 (IL2). The cell surface markers underwent several significant changes. Among them we noted a higher percentage of labeled cells with anti-CD6 and CD7 monoclonal antibodies (moAbs), and a positivity with an anti-CD19 (B4) moAb. The leukemic LGL spontaneously developed a NK activity on K 562 tumor cells, which was not affected under the various T and B cells growth factors because they became more sensitive to IL2; but they were also stimulated by a 50-kilodalton (KD) B cell growth factor (BCGF) factor devoid of any T cell proliferation activity. Together these results gave a better characterization of azurophilic granules containing T chronic lymphocytic leukemia, and enabled the documentation of the differentiation of LGL with NK activity.

Adult↗
PubMed1987

Cloned human CD3- lymphocytes with natural killer-like activity do not express nor rearrange T cell receptor gamma genes.

Here we report the characterization of T cell receptor (TCR) gene activation in 14 CD3- cloned lymphocytes with natural killer-like activity from different origins. No transcription of either alpha or beta or gamma genes is detected in any of these clones. All J beta, C beta clusters are in germ-line configuration. The 5 presently described J gamma loci (J gamma P1, J gamma P, J gamma 1, J gamma P2, J gamma 2) are also in germ-line configuration on each chromosome. These results indicate that several distinct populations of CD3- cloned NK cells do not use gamma gene products as a recognition structure. Perhaps more importantly, these cells do not appear to be engaged in the earliest presently known stage of T lymphocyte differentiation, namely rearrangement at one of the J gamma loci.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Characterization of mononuclear cell subpopulations in normal fetal peripheral blood.

It is now possible to characterize fetal peripheral blood mononuclear cells (FPBMC) from normal fetuses sampled in utero under ultrasound guidance. The surface phenotype of FPBMC from 25 fetuses, between the 20th and the 26th week of gestation, was studied using standard reagents that are known to delineate mononuclear cell subsets in adult peripheral blood. Results were compared with those obtained in neonates (cord blood) and adults. The major subsets of adult PBMC are represented in fetal blood with few qualitative differences: 20% of FPBMC are not recognized, the percentage of T cells is lower with a higher ratio T4/T8, the fraction of cells that express DR molecule is very high, and the distribution of NK antigens is different in fetuses. B cells and monocytes are in equal proportion. This work represents a prerequisite for future functional studies, and provides normal fetal values that will be useful for prenatal diagnosis of congenital immunodeficiency.

Adult↗