A case of acute eosinophilic pneumonia with hypersensitivity to "red spider" allergens.
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Adolescent↗
Biomedical subjects
I Theodorou
Publications and source records attributed to I Theodorou.
Recombination pattern of the TCR gamma locus in human peripheral T-cell lymphomas.
The recombination events of the gamma and beta T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR alpha beta PTCLs, 22/23 cases showed a gamma-gene rearrangement while only 18/23 showed a concomitant beta-gene rearrangement. The germline configuration of the beta locus was found in angiommunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three gamma delta PTCLs rearranged both gamma and beta genes. TCR silent PTCLs showed three different patterns of gamma- and beta-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged gamma and a germline beta locus; and five cases had the two loci rearranged. Regarding the variable genes in the gamma-rearranged alleles, members of the V gamma I subgroup were the most frequently presented (39/50), followed by V gamma II, V gamma III, and V gamma IV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the gamma locus is more frequently rearranged whatever the TCR expression. The gamma-locus analysis provides a better diagnostic yield than the beta locus in the study of PTCL clonality.
Adult↗
CD2 triggering stimulates a phospholipase A2 activity beside the phospholipase C pathway in human T lymphocytes.
In previous studies we demonstrated the triggering of the phospholipase C (PLC) pathway during the activation of an Ag-specific human CD4+ T lymphocyte clone by a mitogenic pair of CD2 (X11,D66) mAb. Similar conditions were applied to investigate a possible involvement of a phospholipase A2 (PLA2) acting as an additional alternative pathway during human T cell activation. Our results show that arachidonic acid or its derivatives are released after CD2 triggering. This release is largely independent of PLC activation and is mediated by a PLA2 because: 1) phosphatidylcholine is the preferential source of [3H]arachidonate release; 2) [3H]arachidonic acid release and phosphatidylcholine hydrolysis are blocked by two inhibitors of solubilized PLA2, mepacrine, and 4-p-bromophenacylbromide; and 3) we evidenced a PLA2 activity in cell homogenates. Extracellular calcium appears to play a critical role because the effects of CD2 mAb were inhibited in a Ca2(+)-depleted medium. In contrast, protein kinase C is not implicated since PMA, a protein kinase C activator, neither stimulated arachidonic acid release nor modulated CD2-induced arachidonic acid release. Cyclic AMP which has been proved to regulate the activity of the PLC in T lymphocytes does not appear to play an important role in the regulation of PLA2 activity since PGE2 has only a minimal effect on [3H]-arachidonate release. Altogether, these findings suggest that CD2 triggering stimulates a PLA2 activity in T lymphocytes via an extracellular Ca2(+)-dependent PLC protein kinase C independent mechanism.
Antigens, Differentiation, T-Lymphocyte↗
A human TCR-Ig chimeric protein used to generate a TCR alpha chain variable region-specific mAb.
In a recent report, a construction containing the alpha chain-variable region (V alpha) coding sequence of a cDNA clone derived from a diphtheria toxoid-specific human T cell (P28), fused to a human immunoglobulin kappa light chain constant region (Ck), was used stably to transfect a murine myeloma cell. In the present study, these transfected cells were employed as an immunogen to raise a mAb, termed 1C5V alpha, specific both for the V alpha Ck chimeric protein secreted by the transfectant and the P28 T cell antigen receptor-V alpha region. mAb 1C5V alpha specifically immunoprecipitates the V alpha Ck protein as a family of 32-35 kDa bands present in the 35S-methionine-labeled culture supernatant from the transfected cells. It specifically binds clone P28. Surface molecules recognized by mAb 1C5V alpha are physically linked to the CD3 molecules since cell treatment with either 1C5V alpha or anti-CD3 mAbs caused the simultaneous down-regulation of the CD3/TCR molecular complex. This link is further supported by immunoprecipitation experiments. Thus, both the 1C5V alpha and the anti-CD3 mAbs precipitate the 16-28 kDa CD3 molecules and the disulfide-linked form of P28 TCR from 125I-labeled P28 T cells. Studies performed in order to define whether a stimulus directly acting on the TCR-V alpha region may trigger the intracellular events observed during human T cell activation showed that (a) mAb 1C5V alpha efficiently triggers the phospholipase C transduction pathway revealed by an accelerated phosphoinositides turn-over and an increased production of phosphorylated derivatives of inositol phosphates; (b) mAb 1C5V alpha induces an up-regulation of IL2R mRNA, accompanied by a slight increase of IL2 and IFN alpha mRNA transcripts evidently amplified in the presence of PMA; (c) soluble mAb 1C5V alpha is strongly mitogenic together with PMA. These results provide the first evidence for the structural authenticity of a secreted water-soluble chimeric form of the variable region of a human TCR alpha chain. They further demonstrate that such chimeric proteins may be valuable tool to further dissect the various functional structure of the human TCR.
Antibodies, Monoclonal↗
Abnormally expanded CD8+/Leu-7+ lymphocytes persisting in long-term bone marrow-transplanted patients are resting pre-cytotoxic T-lymphocytes.
We analyzed the functional status of the small CD8+/Leu-7+ T-lymphocytes that circulate in increased proportions in the blood of many allogeneic bone marrow transplant (BMT) patients. Purified CD8+/Leu-7+ T cells were tested for their effect on T-cell proliferative responses. In contrast to CD8+/Leu-7-T-lymphocytes, such cells behaved as suppressor cells for lectin-induced mitogenic responses of the donor's peripheral blood lymphocytes. However, they did not interfere with the in vitro responsiveness to specific stimuli such as protein purified derivative (PPD) or alloantigens. We demonstrate that CD8+/Leu-7+ T cells are resting pre-cytotoxic T-lymphocytes (CTL) that can be induced by mitogenic lectins to express their cytolytic program in a non-specific, non-major histocompatibility complex-restricted manner against phytohemagglutinin-treated lymphoblasts or K562 target cells. The lectin-triggered cytotoxicity was achieved within a few days, together with limited cell division. Our results suggest that circulating CD8+/Leu-7+ T cells from BMT recipients are in vivo primed CTL awaiting cellular activation.
Antigens, CD↗
Cell-mediated suppression of HIV-specific cytotoxic T lymphocytes.
CTL specific for HIV have been described in lungs of infected patients at early stages of HIV disease. In order to characterize the evolution over time of HIV-specific CTL, we have analyzed the cytotoxic function and the cell surface phenotype of the alveolar lymphocytes from 41 patients at various stages of HIV disease. We demonstrated a progressive decline of alveolar anti-HIV CTL activity and detected Ts cells from the lungs of patients with advanced HIV disease. These alveolar T cells strongly suppressed the effector phase of anti-HIV CTL lysis. They lacked a marked specificity of function because they also block anti-HLA CTL response and were not restricted by the HLA-class-I transplantation Ag. They displayed the CD3, CD8, and HNK1 markers, were CD4 and CD16 negative, and lacked NK activity. The presence of Ts cells at late stages of HIV disease could thus partly explain the inefficiency of host defenses against HIV.
AIDS-Related Complex↗
Impact of genetically regulated T cell proliferation on acquired resistance to Listeria monocytogenes.
Two lines of mice genetically selected for high and low in vitro responses to PHA were used to evaluate the impact of T cell polyclonal expansion on acquired resistance to Listeria monocytogenes. The selective breeding induced two major consequences in low responder mice: (1) a reduction of the number of L3T4+ cells and (2) a restriction of T cell expansion upon PHA stimulation, predominantly affecting the Lyt-2+ subset, and associated with an abridgment of IL-2 production. In vivo PHA stimulation induced anti-Listeria protection in high responder mice, but was much less effective in low responder mice. Flow cytometer analysis revealed that T cell proliferation was also reduced in low responder mice during the course of Listeria infection, implying both L3T4+ and Lyt-2+ subsets. This defect did not apparently influence the kinetics of bacterial elimination in host tissues, which was similar in both lines during primary Listeria infection. In contrast, the expression of delayed-type hypersensitivity to Listeria antigens and the level of immunologic memory were significantly reduced in low responder mice. In vivo selective T cell depletion by anti-L3T4 or anti-Lyt-2 mAb allowed us to demonstrate the predominant role of Lyt-2+ cells in protection and that of L3T4+ cells in the expression of delayed-type hypersensitivity.
Animals↗
Phenotype and function of peripheral blood and bone marrow T-cell colonies: identification of DC3-, 4-, 8-autoreactive T cells.
The existence of immature autoreactive T cells has been examined in peripheral blood (PB) and bone marrow (BM) derived T-lymphocyte colonies (TLC) that have previously been shown to be potentially generated from CD3-negative BM-T cells. An extensive phenotypical analysis of total and T-depleted TLC showed that both PB- and BM-derived TLC contained a mean of 5% immature T lymphocytes (ITL), which were negative for the CD3, CD4, and CD8 antigens but displayed the CD2 and CD7 antigens. The only detectable immune functions of these isolated ITL were an allo- and an autoreactivity without cytolytic activity. The self-reactivity of ITL was not detected in bulk non T-depleted TLC cells and seemed to be actively suppressed by autologous mature T cells. In addition, the auto-MLR of ITL was totally inhibited by anti-HLA class II but not by anti-class I monoclonal antibody (MoAb) and only partially by anti-CD4 moAb, whereas the anti-CD3 and anti-CD2 MoAbs gave no inhibition. Once activated, ITL could acquire in culture a mature T cell CD3 + CD4 + phenotype. The CD3-, 4-, 8-auto-reactive T cells present in T colonies could represent pre- or post-thymic cells that have not yet undergo or that have escaped the thymic selection.
Antigens, Differentiation, T-Lymphocyte↗
T-cell nonmalignant clonal proliferation in ataxia telangiectasia: a cytological, immunological, and molecular characterization.
Cytogenetically abnormal T-cell nonmalignant clones are a characteristic feature of ataxia telangiectasia (AT). Here, we study a t(14;14) clone from a patient with AT, and provide a cytological, immunological, and molecular characterization. This cellular population is clonal at the molecular level, but is phenotypically heterogeneous, with CD4+CD8+ and CD4-CD8+ cells. Although these cells do not divide in the peripheral blood, a majority of them are found in G1 phase and express the membrane antigen 4F2, a very early marker of activation. Many similarities are found between this nonmalignant AT clone and T-cell prolymphocytic leukemia at the morphologic, cytogenetic, and immunologic levels, despite the different clinical courses associated with these proliferations. We hypothesize that the t(14;14) translocation is linked to the abnormal morphology and immunophenotype of the AT clone cells, but that this translocation confers only a preactivated state to the cells. A complete malignant transformation would then be due to secondary events.
Adolescent↗
PGE2-induced cyclic AMP accumulation in human CD4+ T cells is strongly enhanced during the CD2-mediated activatory process.
The effect of a mitogenic combination of two different anti-CD2 monoclonal antibodies on the PGE2-stimulated and basal cAMP production in human CD4+ T cell clones was investigated. The anti-CD2 stimulation strongly potentiates the PGE2-induced cAMP production while both PMA and A23187 produced a less potent effect. On the opposite the anti-CD2 treatment is without any effect on the basal cAMP level contrasting with a marked increase of intracellular cAMP concentrations with A23187 or the combination of A23187 and PMA. These results suggest that activation of CD4+ human T cells via the CD2 molecule significantly influences the cAMP-related transduction pathway. Although PMA and A23187 also modulate the activity of this pathway, their effect in this model is more likely mediated through an amplification of basal cAMP production.
Antibodies, Monoclonal↗
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↗
Cyclic AMP-mediated alteration of the CD2 activation process in human T lymphocytes. Preferential inhibition of the phosphoinositide cycle-related transduction pathway.
Activation of human T lymphocytes via the CD2 molecule produces an enhanced turnover of phosphatidylinositol (PI) cycle-related phospholipids accompanied by the increased production of diacylglycerol (DG) and phosphorylated derivatives of inositol (IP). In this report we demonstrate that increased levels of intracellular cyclic AMP induced in human T lymphocytes by prostaglandin E2 or dibutyryl cAMP antagonize these early biochemical events of the CD2 activation process. Thus, a substantial inhibition of the CD2-induced increase in 32P-phosphatidic acid and 32P-PI values is observed. In parallel, both the DG production and the IP release triggered by the CD2 signal are strongly reduced contrasting with an almost conserved Ca2+ response. We also report here that cAMP does inhibit the CD2-induced proliferation in a dose-dependent manner while the proliferation generated independently of DG and IP production by a combination of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate is not affected. These results therefore suggest that (a) intracellular cAMP levels may participate in the regulation of the PI cycle-related transduction pathway involved in the activation process of human T lymphocytes via the CD2 molecule; (b) the observed cAMP-mediated functional inhibitory effects are mainly related to an alteration of this cellular transduction signal; and (c) considering the putative critical second messenger role in the T cell proliferative response of DG and IP, respectively thought to activate the protein kinase C and to raise the intracellular free Ca2+, the lowering of DG production may be the key event responsible for this cAMP-mediated effect.
Adenylyl Cyclases↗
Distribution of the CCR5 gene 32 base pair deletion and SDF1-3'A variant in healthy individuals from different populations.
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Base Pairing↗
MIC genes in non-human primates.
MIC molecules belong to the immunoglobulin superfamily, are encoded within the MHC region and are recognized by gamma/delta T-cell receptors. In humans, at least two functional genes (MIC-A* and MIC-B*) and two pseudogenes (MIC-C* and MIC-D*) exist. Functional MIC gene copies are characterized by a high degree of polymorphism, while pseudogenes bear several debilitating mutations either in the putative extracellular region or in the transmembrane region of the molecule. In this study we sequenced these segments of MIC genes in seven non-human primates in order to determine whether debilitating mutations were present. All the MIC primate genes studied were highly homologous to their human counterparts, and cystein residues involved in the maintenance of the immunoglobulin-like structure were highly conserved. Furthermore, none of the MIC genes studied contained stop codons in the extracellular or transmembrane segments of the molecule, which suggests that at least one functional gene copy exists in non-human primates. A distinct family of MHC immunoglobulin-like genes was recently identified within the MHC class I region in humans (Bahram et al., 1994; Leelayuwat et al., 1994). Members of this MIC (MHC class I chain related) gene family belong to the immunoglobulin superfamily. Similar to classical class I MHC genes, they are characterized by three distinct extracellular domains (alpha 1-3), a transmembrane (TM) segment and a cytoplasmic segment, each encoded by a separate exon (Bahram et al., 1994; Bahram et al., 1996). Other similarities between MIC genes and classical MHC genes include a high degree of polymorphism (Fodil et al., 1996; Pellet et al., 1997) and recognition by T-cell receptors (Groh et al., 1998). These findings suggest that the putative MIC-A* chain has evolved for a function that is related to, but quite distinct from, that of typical MHC class I chains.
Amino Acid Sequence↗