bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the CD3/T cell receptor (TcR) complex or of protein kinase C potentiate adenylyl cyclase stimulation in a tumoral T cell line: involvement of two distinct intracellular pathways
Authors: Bihoreau Claire , Heurtier Agnès , Enjalbert Alain , Corvaïa Nicole , Bensussan Armand , Degos Laurent , Kordon Claude 
Published: March 2007

AbstractA monoclonal antibody (OKT3) directed against the T cell receptor (TcR)/CD3 molecular complex, as well as a protein kinase C (PKC) activator (phorbol 12‐myristate 13‐acetate, PMA) were added to a culture of tumoral Jurkat T cells, in order to precise the sequence of intracellular signals leading to T cell activation. The experiments were performed in the presence or in absence of various stimulators of adenylate cyclase (AC) such as forskolin (FK), cholera toxin (CT) or prostaglandin E2 (PGE2). OKT3 increased inositol phosphate (IP) production; in parallel, it induced a slight accumulation of cAMP. The effect was markedly potentiated in presence of FK or CT, and to a lesser extent in the presence of PGE2. FK stimulated adenylate cyclase of Jurkat cell membranes, but the effect was not potentiated by OKT3, suggesting that potentiation of cAMP accumulation requires intact cells and is not mediated by direct receptor coupling. On the other hand, elevated cAMP accumulation induced a negative feedback on IP production. The effect of OKT3 on cAMP was mimicked by A23187, a Ca2+ ionophore, and abolished in the absence of extracellular Ca2+. PMA had the same effect as OKT3 on basal or FK‐ and CT‐induced accumulation of cAMP. In contrast, it inhibited the PGE2 effect on the cyclic nucleotide. After desensitization of PKC by pretreatment with a high concentration of PMA, the phorbol ester was no longer effective. Under those conditions, facilitation by OKT3 of FK‐induced accumulation of cAMP was preserved, whereas potentiation by the monoclonal antibody of the PGE2 stimulation of AC was even enhanced. The data indicate that cAMP accumulation indirectly elicited by phospholipase C activation is, at least partly, mediated by IP‐dependent Ca2+ mobilization, while PKC is preferentially effective as an inhibitor of PGE2 stimulation.
Recombinant soluble tumor necrosis factor receptor proteins protect mice from lipopolysaccharide‐induced lethality
Authors: Lesslauer Werner , Tabuchi Hisahiro , Gentz Reiner , Brockhaus Manfred , Schlaeger Ernst Juergen , Grau Georges , Piguet Pierre Francois , Pointaire Pascal , Vassalli Pierre , Loetscher Hunsruedi 
Published: March 2007

AbstractThe in vivo efficacy of human recombinant soluble tumor necrosis factor (TNF) receptor protein to prevent and to treat lipopolysaccharide (LPS)‐induced lethal toxicity in D‐galactosamine‐treated mice was investigated. Chimeric proteins of the receptor extracellular domains fused to the hinge region of human IgG3 were expressed in myeloma cells (rsTNFR‐hγ3). The fusion proteins had a disulfide‐bonded dimeric structure. Upon intravenous injection, their serum concentration decreased relatively slowly after an initial phase of rapid elimination. D‐galactosamine‐sensitized mice were fully protected from the toxic effects of LPS, if the animal were pretreated with rsTNFR‐hγ3 at 20 μg/animal. Partial protection was seen at significantly lower doses and when rsTNFR‐hγ3 was given up to 3 h after LPS.
Therapy against murine collagen‐induced arthritis with T cell receptor Vβ‐specific antibodies
Authors: Chiocchia Gilles , Boissier Marie‐Christophe , Fournier Catherine 
Published: March 2007

AbstractImmunization with native type II collagen (CII) of susceptible strains of mice (H‐2q) induces a rheumatoid arthritis‐like disease. Collagen‐induced arthritis (CIA) is an experimental model for T cell‐mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII‐primed DBA/1 mice were treated with various TcR VbT‐specific monoclonal antibodies (mAb) using a protocol resulting in a long‐term elimination of the target T cells. In vivo treatment with anti‐CD4 mAb led to nearly complete protection against CIA. Mice injected with anti‐Vβ8.1,2 or anti‐Vβ5.1,2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti‐VbT2 mAb delayed the onset of the disease whereas injection of anti‐VbT6 or anti‐VbT11 mAb did not alter CIA. Moreover, the combined treatment with anti‐VbT2 and anti‐Vβ5 mAb efficiently reduced the development of CIA. The humoral response to CII was down‐regulated only in the groups of mice that were improved by the treatment. In vitro proliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti‐VbT mAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA express a limited number of Vβ chains.
Direct interaction with primed CD4+ CD45R0+ memory T lymphocytes induces expression of endothelial leukocyte adhesion molecule‐1 and vascular cell adhesion molecule‐1 on the surface of vascular endothelial cells
Authors: Damle Nitin K. , Eberhardt Chris , Van Der Vieren Monica 
Published: March 2007

AbstractThe process of recruitment of leukocytes at sites of inflammation involves direct cell‐to‐cell interactions between leukocytes and vascular endothelial cells (EC) mediated by various adhesion receptors on leukocytes and their inducible endothelial ligands. In this study we have examined the induction on EC of endothelial leukocyte adhesion molecule‐1 (ELAM‐1), intercellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule‐1 (VCAM‐1) upon their interaction with subpopulations of human T cells. When co‐cultured with EC both resting CD4+ T and CD8+ T cells caused a modest increase in the expression of endothelial ICAM‐1. Moreover, resting CD4+ but not CD8+ T cells induced expression of ELAM‐1 and VCAM‐1 on a small fraction of unstimulated EC. Prior activation with phorbol 12‐myristate 13‐acetate (PMA) significantly increased the ability of T cells to up‐regulate endothelial ICAM‐1 and also induced the expression of both ELAM‐1 and VCAM‐1. PMA‐primed CD4+ T cells induced both VCAM‐1 and ELAM‐1 on EC more efficiently than CD8+ T cells. Furthermore, the ability to induce the expression of ELAM‐1 and VCAM‐1 was confined to the CD4+CD45R0+ memory/primed subpopulation of T cells. This induction of various endothelial adhesion ligands could also be mediated by antigen‐primed CD4+ T cell lines. The CD4+ T cell‐mediated induction of adhesion ligands required direct intercellular contact with EC because neither cultures of EC and PMA‐primed CD4+ T cells separated by a microporous membrane insert nor the conditioned medium of PMA‐primed T cells induced expression of ELAM‐1 and VCAM‐1 on EC. Cyclosporin A significantly inhibited the activation of T cells with PMA but had no effect on the ability of PMA‐primed T cells to up‐regulate endothelial CAM. Thus, CD4+CD45R0+ T cells via as yet unknown mechanism can significantly enhance the expression of each of the three endothelial adhesion ligands and, thereby, may facilitate the process of recruitment of additional leukocytes to exacerbate inflammation.
Environmental and allele‐specific influences on T cell receptor gene rearrangement: skewed α, δ and γ gene rearrangement patterns in chimeric mice
Authors: Larché Mark , Manzo Andrea R. , Hurwitz Julia L. 
Published: March 2007

AbstractThis study was performed as a means to examine the effects of environment and stem cell origin on the molding of T cell receptor gene rearrangements during T cell development. Lethally irradiated adult mice were first reconstituted with (C57BL/6 x DBA/2)F1 stem cells, which derived either from a fetal liver or adult bone marrow source. The gene rearrangements in the irradiated thymi were then compared to those in normal fetal or adult thymi by hybridoma analysis. Results showed a general absence of gene rearrangements typical of the normal fetal thymus in both sets of chimeras, α and γ gene rearrangements in chimeric mice matched normal adult patterns. However, chimeric thymocytes were unique in an unusually low frequency of rearrangements at the δ locus. The use of the bone marrow vs. fetal liver as stem cell sources in chimeric mice did not affect the patterns, indicating that environmental factors played a major role in the molding of gene rearrangement at multiple T cell receptor loci. Interestingly, the chromosomal sequence added an additional influence as homologous chromosomes showed allele‐specific rearrangement patterns. We now question whether the unique patterns of rearrangement in irradiated adult thymi may substantially affect developing T cell populations in chimeric animals, particularly with regard to the γ/δ T cell subset. Further analyses are warranted, both in experimental and clinical settings, regarding ultimate potentials for T cell diversity and function in transplantation recipients.
An abnormal signal transduction pathway in CD4−CD8− double‐negative lymph node cells of MRL lpr/lpr mice
Authors: Yokoyama Kazushige , Gachelin Gabriel 
Published: March 2007

AbstractWe describe here a novel 26‐kDa posphoprotein (p26), associated to the T cell receptor of CD4−CD8− lymph node cells of lpr/lpr mice, but not present in significant amounts in control mouse cells including polyclonally activated T cells. lpr p26 is constitutively phosphorylated on a tyrosyl residue. It is most likely a member of the G protein family and displays high GTP‐binding and GTPase activities both unsensitive to interleukin 2. Bordetella pertussis toxin has no effect on the spontaneously enhanced GTP hydrolysis. The traits associated to p26 could contribute to the distinctive features of lpr/lpr double‐negative cells.
Down‐regulation by tumor necrosis factor‐α of neutrophil cell surface expression of the sialophorin CD43 and the hyaluronate receptor CD44 through a proteolytic mechanism
Authors: Campanero Miguel R. , Pulido Rafael , Alonso Jose L. , Pivel Juan P. , Pimentel‐Muiños Felipe X. , Fresno Manuel , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractAdhesion of human neutrophils to endothelial cells is a crucial step during migration to the extravascular sites of inflammation. A large number of molecules, including the CD44 and LAM‐1 antigens, have been described to participate in this process. We have investigated the regulation by human recombinant tumor necrosis factor‐α (TNF‐α) of human neutrophil plasma membrane expression of both CD44 and LAM‐1 adhesion molecules, as well as that of CD43 sialophorin, which has been involved in adhesion and activation of leukocytes. The expression of these three antigens was down‐regulated in neutrophils upon TNF‐α treatment, as determimned by immunofluorescence and immunoprecipitation expriments. However, the expression of other cell surface molecules, such as CD45 or CD11b, was up‐regulated. Similar regulatory effects were also observed upon neutrophil treatment with other activating agents such as the chemoattractant peptide formyl‐Met‐Leu‐Phe, the calcium ionophore A23187, or the phorbol ester phorbol 12‐myristate 13‐acetate. Protease inhibitors virtually abrogated the TNF‐α‐induced down‐regulation of CD43 and CD44 expression, but not that of LAM‐1, suggesting the involvement of a protease activity in this process. These results underline the role of TNF‐α on the differential regulation of cell surface expression of neutrophil adhesion molecules, thus implying modifications in the neutrophil adhesive properties.
Prolonged survival of skin grafts following treatment with an antibody to a putative cell triggering molecule, QCA‐1
Authors: Aspinall Richard , Kampinga Jaap , Van Den Bogaerde Johan 
Published: March 2007

AbstractThe QCA‐1 molecule (quiescent cell antigen‐1) appears to be involved in the differentiation events undergone by T cell following occupancy of the antigen receptor. Here we show that modulation of the QCA‐1 antigen from the surface of the cell normally follows activation, and that treatment of animals with the antibodies against the QCA‐1 molecule inhibits the normal response to an allograft without appearing to alter the number of peripheral T cells or the expression by these cells of the α/β T cell antigen receptor.
Differential responses to interleukin 2 define functionally distinct subsets of human natural killer cells
Authors: Baume Daniel M. , Robertson Michael J. , Levine Herbert , Manley Thomas J. , Schow Peter W. , Ritz Jerome 
Published: March 2007

AbstractHuman natural killer (NK) cells can be subdivided into two populations based on the density of cell surface CD56 antigen. The great majority (∼ 90%) of NK cells express CD56 at low levels (the CD56dim phenotype), whereas a small NK cell subset (∼ 10%) exhibits approximately fivefold greater density of surface CD56. Exposure to exogenous interleukin 2 (IL 2) induces tenfold greater proliferation of CD56bright cells compared to CD56dim lymphocytes, even though both subsets constitutively express similar levels of intermediate affinity IL 2 receptor (IL 2R) p75 chains. Incubation with IL 2 alone or irradiated target cells alone could induce expression of the IL 2R p55 chain by both CD56bright and CD56dim NK cells; a combination of both stimuli was most effective. IL 2R p55 induction was evident after co‐culture of NK cells with both NK‐sensitive and NK‐resistant cell lines or with antibody‐coated target cells. Activation of NK cells with IL 2 plus target cells resulted in enhanced proliferation compared to activation with IL 2 alone; target cells alone did not induce significant proliferation. Although both NK cell subsets appeared to express high‐affinity IL 2R p75/p55 heterodimers after stimulation with target cells and IL 2, proliferation of CD56dim cells remained minimal after such activation; activated CD56dim cells consistently demonstrated less proliferation to IL 2 than did resting CD56bright cells. In contrast, CD56bright NK cells exhibited even greater proliferation after stimulation with target cells. Almost all CD56dim NK cells expressed CD16 (FcγR III) as well as the NK ζ chain, whereas <50% of CD56bright cells express either CD16 or ζ. CD56bright and CD56dim lymphocytes, thus, appear to represent distinct subpopulations of NK cells with different functional activities. Unlike CD56bright cells, CD56dim NK cells do not proliferate optimally to IL 2, even after the latter have been stimulated to express both IL 2R p55 and IL 2R p75. Efficient proliferation of CD56dim NK cells may, thus, require additional or alternative signals.
Intestinal intraepithelial lymphocyte T cells are resistant to Ipr gene‐induced T cell abnormalities
Authors: Aicher Wilhelm K. , Fujihashi Kohtaro , Taguchi Takashi , McGhee Jerry R. , Yamamoto Masafumi , Eldridge John H. , Gay Steffen , Kiyono Hiroshi 
Published: March 2007

AbstractThe mucosal immune system of the gastrointestinal (GI) tract consists of Peyer's patches (PP), which are IgA inductive sites, and more diffuse effector regions which include cells in the intraepithelial lymphocyte (IEL) compartment. Since autoimmune MRL lpr/lpr (MRL/lpr) mice develop a proliferating CD3+, CD4−, CD8− (double negative; DN), B220+ T cell subset in systemic lymphoid tissue, we have initiated studies to determine the distribution of CD3+, DN, B220+ T cells (B220+ T cells or lpr/lpr T cells) in the GI immune system. Specifically, we examined T cell subsets separated according to expression of CD4, CD8, Thy‐1, B220, α/β T cell receptor (TcR) and γ/δ TcR in PP and IEL of MRL/lpr mice at 6, 12 and 21 weeks of age. Increased numbers of CD3+ T cells were noted in both PP and spleen of 12‐ and 21‐week‐old mice in which the development of autoimmune disorders were also evident. However, normal numbers of CD3+ IEL T cells were seen in MRL/lpr mice in all three age groups tested. When the presence of T cell lymphadenopathy was examined in both IgA inductive and effector tissues, the PP followed the B220+ T cell pattern seen in the spleen, where ∼ 30%‐50% of CD3+ T cells in the PP of 12‐ and 21‐week‐old MRL/lpr mice expressed the phenotype of lpr/lpr T cells and >90% were α/β TcR+. On the other hand, B220+ T cells had not developed in PP or spleen of 6‐week‐old MRL/lpr mice. Of interest was the finding that IEL from lpr/lpr homozygous mice did not contain B220+ T cells in any age group tested. In this regard, the IEL of MRL/lpr mice comprised an identical pattern and frequency of CD4−/CD8−, CD4+/CD8−, DN and CD4+/CD8+ (double positive, DP) T cell subsets as their normal counterparts (i.e. MRL +/+, BALB/c and C3H/HeN mice) which consisted of ∼75%, ∼7.5%, ∼7.5% and ∼10%, respectively. Further, Thy‐1, γ/λ TcR and α/β TcR expression in these four subsets of MRL/lpr IEL were very similar to normal mice. These results suggest that the intestinal IEL compartment is minimally affected by the lpr/lpr mutation which induces T cell abnormalities and indicate that B220+ T cells do not preferentially home to IEL. Further, our results support the concept that IEL T cells develop as a separate T cell lineage from thymus‐derived cells.
ICAM‐1‐independent lymphocyte transmigration across high endothelium : Differential up‐regulation by interferon γ, tumor necrosis factor‐α and interleukin 1β
Authors: May Michael J. , Ager Ann 
Published: March 2007

AbstractThe adhesion of lymphocytes to cytokine‐treated high endothelium was studied using cultured high endothelial cells (HEC). Pretreatment of the HEC layer with a variety of cytokines caused up‐regulation of lymphocyte adhesion with the effects ordered interferon γ (IFN‐γ) > tumor necrosis factor‐α (TNF‐α) ⩾ interleukin 1β (IL 1β). Increased lymphocyte adhesion was found to be independent of ICAM‐1 as expression by HEC was not increased by cytokines and antibodies against ICAM‐1 did not block adhesion. The peptide CS1 and anti‐β1 integrin subunit antibodies, however, caused partial inhibition of lymphocyte adhesion thus indicating a role for fibronectin on HEC and α1β1 on lymphocytes. Study of the kinetics of lymphocyte adhesion showed that the effects of IFN‐γ and TNF‐α were persistent and remained detectable 2.5 h after removal of the cytokines whereas the effects of IL 1β were transient and were not sustained beyond 1 h. All of the cytokines used caused transient increases in the number of surface‐bound lymphocytes with IFN‐γ > TNF‐α ⩾ IL 1β, however, the most dramatic effect was on the transmigration of lymphocytes across the HEC. Both IFN‐γ and TNF‐α caused sustained increased transmigration with IFN‐γ having the greater effect. IL 1β had little effect on transmigration. This model demonstrates that the binding and transmigration of lymphocytes across HEC can be differentially regulated by the actions of individual cytokines. These results support the concept that locally produced cytokines regulate HEC function within the lymph node.
The human cord blood antibody repertoire. Frequent usage of the VH7 gene family
Authors: Mortari Frank , Newton J. Allen , Wang Jin Yi , Schroeder Harry W. 
Published: March 2007

AbstractWe have previously demonstrated a consistent preferential usage of a small set of VH, DH and JH gene segments in second‐trimester fetal liver. To examine the extent of heavy chain repertoire diversification in newborns, we generated an unrestricted cDNA library from cord blood mononuclear cells and sequenced the variable domains of randomly isolated Cμ+ transcripts. We found this set of transcripts to be enriched for JH4, 5 and 6, whereas previously reported fetal transcripts preferentially expressed JH3 and 4. The cord blood transcripts used a number of different DH gene segments, whereas fetal transcripts were enriched for DHQ52. Of the thirteen cord blood sequenced, three were members of the newly described VH7 family which to date has not been detected in fetal liver. Indeed, only one of the isolated VH gene segments had been previously observed in fetal transcripts. As a result of enhanced N‐region addition and use of longer DH and JH gene segments, both the sequence diversity and range of potential antigen‐binding structures of cord blood complementarity‐determining region 3 domains was vastly expanded. Thus, the repertoire bias evident in fetal liver was no longer apparent in this more mature population of cord blood B cells.
A major human thyroglobulin epitope defined with monoclonal antibodies is mainly recognized by human autoantibodies
Authors: Henry Mireille , Zanelli Eric , Piechaczyk Martine , Pau Bernard , Malthièry Yves 
Published: March 2007

AbstractThe antigenic nature of 15 anti‐human thyroglobulin (hTg) monoclonal antibody (mAb) epitopes was studied by two different approaches. First, we tested two successive protease‐digest products of hTg. Only four mAb from the same cluster of reactivity recognized a low‐molecular weight peptide, the other mAb only bound native hTg or high‐molecular weight digest fractions. Second, these 15 mAb were used to immunoscreen hTg expression libraries. Only the same four mAb revealed immunoreactive clones corresponding to region 1149–1295 on the hTg primary sequence. After subcloning, this antigenic determinant was reduced to a 102‐amino acid peptide (hTg region 1149–1250). The two different methodologies were coherent and complementary, and demonstrated that hTg sequence 1149‐1250 is the target for this cluster of four mAb. Moreover, anti‐hTg autoantibodies which cross‐reacted with these mAb bound the 102‐amino acid peptide. This epitope was the one most frequently detected by sera from autoimmune thyroid disease. The data confirm the presence of an immunodom‐inant domain in the central part of the hTg molecule and suggest that this mAb epitope may be a powerful probe for the diagnosis of autoimmune thyroid disorders.
Cyclosporin A can switch the immune response induced by antigen from a humoral to a cell‐mediated mode
Authors: Bretscher Peter A. , Havele Calliopi 
Published: March 2007

AbstractCyclosporin A (CsA) is known as a nontoxic inhibitor of the immune response that is primarily employed in humans to prevent the rejection of allografts. We report here on a novel activity for this drug as an immunomodulator. CsA can either inhibit or facilitate the induction of delayed‐type hypersensitivity (DTH) depending on the class of immune response that would be induced in the absence of the drug. The drug inhibits the in vivo and in vitro induction of DTH when antigen is given under conditions that normally result in the induction of this response. The same concentration or dose of CsA inhibits the in vitro and in vivo induction of an antibody response and the antigen induces DTH instead. An explanation for these different effects of CsA on the induction of DTH is proposed. This novel activity of CsA in modulating the immune response from an antibody to a cell‐mediated mode may have clinical applications.