bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell sensitivity to HLA class I‐mediated apoptosis is dependent on interleukin‐2 and interleukin‐4
Authors: Genestier Laurent , Paillot Romain , Bonnefoy‐Berard Nathalie , Waldmann Herman , Revillard Jean‐Pierre 
Published: March 2007

AbstractAntibody interaction with a specific epitope of the HLA class I α1 domain triggers apoptosis of activated but not resting T and B cells by a pathway which involves neither Fas ligand nor tumor necrosis factor‐α. We have investigated at which stage of activation and proliferation T cells become sensitive to HLA class I‐mediated apoptosis, using two monoclonal antibodies (mAb) which recognize the same monomorphic epitope of the HLA class I α1 domain (mAb90, mouse IgG1, and YTH862, rat IgG2b) and can induce apoptosis of phytohemagglutinin (PHA)‐activated peripheral blood lymphocytes. Sensitivity to apoptosis develops after the expression of G1 markers (CD69 expression) but it is accelerated by addition of recombinant interleukin‐2 (rIL‐2). Blocking the IL‐2 pathway by cyclosporin A, FK506, rapamycin, anti‐IL‐2 or CD25 antibodies, prevented the development of sensitivity to apoptosis. Addition of IL‐2 and, to a lesser extent, IL‐4, reversed the inhibitory effect of cyclosporin A. Conversely, rIL‐7 and recombinant interferon‐γ restored proliferation of peripheral blood lymphocytes stimulated by PHA in the presence of cyclosporin A but did not restore sensitivity to class I‐mediated apoptosis. Finally cells stimulated in the presence of the DNA polymerase inhibitor aphidicolin did not enter into S phase of the cell cycle but secreted IL‐2 and underwent apoptosis when exposed to mAb90 or YTH862. Together, the data indicate that sensitivity of peripheral T cells to HLA class I‐mediated apoptosis depends on both activation signals and IL‐2 or IL‐4, but does not require cell proliferation. These data suggest that YTH862 and mAb90 might be used for achieving clonal deletion of antigen‐activated peripheral T cells in vivo, provided that the IL‐2 pathway is not blocked by other immunosuppressive agents.
A novel subset of adult γδ thymocytes that secretes a distinct pattern of cytokines and expresses a very restricted T cell receptor repertoire
Authors: Azuara Véronique , Levraud Jean‐Pierre , Lembezat Marie‐Pierre , Pereira Pablo 
Published: March 2007

AbstractWe have characterized the function, phenotype, ontogenic development, and T cell receptor (TCR) repertoire of a subpopulation of γδ thymocytes, initially defined by expressing low levels of Thy‐1, that represents around 5 % and 30 % of total γδ thymocytes in adult C57BL/6 and DBA/2 mice, respectively. Activation of FACS‐sorted Thy‐1dull γδ thymocytes from DBA/2 mice with anti‐γδ monoclonal antibodies in the presence of interleukin‐2 (IL‐2) results in the secretion of high levels of several cytokines, including interferon‐γ (IFN‐γ), IL‐4, IL‐10, and IL‐3. In contrast, only IFN‐γ was detected in parallel cultures of Thy‐1bright γδ thymocytes. Virtually all Thy‐1dull γδ thymocytes express high levels of CD44 and low levels of the heat‐stable antigen and CD62 ligand, while around half of them express the NK1.1 marker. Thy‐1dull γδ thymocytes are barely detectable in newborn animals, and their representation increases considerably during the first 2 weeks of postnatal life. The majority of Thy‐1dull γδ thymocytes from DBA/2 mice express TCR encoded by the Vγ1 gene and a novel Vδ6 gene named Vδ6.4. Sequence analysis of these functionally rearranged γ and δ genes revealed highly restricted Vδ‐Dδ‐Jδ junctions, and somewhat more diverse Vγ‐Jγ junctions. We conclude that Thy‐1dull γδ thymocytes exhibit properties that are equivalent to those of natural killer TCRαβ T cells. Both cell populations produce the same distinct pattern of cytokines upon activation, share a number of phenotypic markers originally defined for activated or memory T cells, display similar postnatal kinetics of appearance in the thymus and express a very restricted TCR repertoire.
Regulatory role of CD95 ligation on human B cells induced in vivo capable of spontaneous and highrate Ig secretion
Authors: Medina Francisco , Segundo Carmen , Rodríguez Carmen , Brieva José A. 
Published: March 2007

AbstractCD95 ligation elicits apoptotic signals in many cell systems. This study analyzes the effect of anti‐CD95 mAb on human cells capable of spontaneous and highrate Ig secretion. Such cells have been induced in vivo and represent a highly mature B cell stage. Addition of the anti‐CD95 monoclonal antibody (mAb) CH11 to tonsil B cells inhibited 50–60% of their spontaneous Ig secretion. The effect was exerted early in the culture and could be reversed by a pre‐treatment with a neutralizing mAb. N‐acetyl‐D‐sphingosine (C2‐ceramide), although not a close analog, also reduced Ig secretion to a similar extent. The inclusion of a tetrapeptide inhibitor for certain interleukin‐1β‐converting enzyme proteases prevented the inhibitory effect of CH11 mAb on tonsil B cells. B cells capable of spontaneous Ab secretion obtained from blood of recently‐immunized volunteers were also inhibited by CH11 mAb and C2‐ceramide. In contrast, bone marrow (BM) B cells capable of spontaneous Ig secretion were unaffected by these agents. This CD95 ligation‐mediated inhibition of tonsil and blood Ig‐secreting B cells could not be reversed by cytokines with demonstrated activity on these B cells. Human mature B cells induced in vivo are identifiable as CD38hi cells. Flow cytometric analysis revealed that a fraction of tonsil CD38hi cells expressed low levels of CD95. Moreover, about 20% of these cells exhibited basal apoptosis, as defined by annexin V binding. This phenomenon was markedly increased by CD95 ligation. On the other hand, BM CD38hi cells showed neither CD95 expression nor CD95‐induced annexin V binding. These data suggest that CD95 ligation might play a role in the control of human humoral responses by inducing apoptosis in susceptible mature B cells.
Maternal IgG stimulates B lineage cell development in the progeny
Authors: Malanchère Evelyne , Huetz François , Coutinho Antonio 
Published: March 2007

AbstractTo examine the physiological role of maternal natural IgG antibodies on the development of B lineage cells of the progeny, we have bred homozygous μMT/μMT or heterozygous μMT/+ females to μMT/μMT or μMT/+ males, respectively. We could thus compare normal or B cell‐deficient mice born from Ig‐deprived (Ig−) or phenotypically normal mothers (Ig+). B cell‐deficient progeny of heterozygous mothers contain no detectable serum IgA or IgM, but IgG concentrations that peak at 2 mg/ml by 7–21 days of age, decay after weaning with a half‐life of 7 days, and remain detectable for 2 months after birth. At 7 days after birth, μMT/+ progeny born of Ig+ mothers contain two‐ to threefold higher numbers of bone marrow (BM) pre‐B and B cells, and of splenic B cells, compared to mice of the same age born from Ig− mothers. In contrast, the former progeny exhibit two to four times lower numbers of Ig‐secreting plasma cells in spleen and thymus, and contain sixfold lower serum IgM concentrations. A similar maternal IgG‐dependent stimulation of BM B cell precursors is also observed in μMT/μMT progeny. No significant differences were detected between the groups on day 3 after birth, suggesting the requirement for a minimal IgG concentration in the serum.
Expression and regulation of monocyte chemoattractant protein‐1 by human eosinophils
Authors: Izumi Shinyu , Hirai Koichi , Miyamasu Misato , Takahashi Yuichi , Misaki Yoshikata , Takaishi Toshiaki , Morita Yutaka , Matsushima Kouji , Ida Nobuo , Nakamura Haruji , Kasahara Tadashi , Ito Koji 
Published: March 2007

AbstractSeveral recent studies have identified eosinophils as a cellular source of various cytokines, indicating that eosinophils play not only an effector role, but also a regulatory role within the allergic inflammatory cell network. In this study, we demonstrate that eosinophils can generate and secrete monocyte chemoattractant protein‐1 (MCP‐1), a prototype of C‐C chemokines. Eosinophils generated immunoreactive MCP‐1 in response to such diverse stimuli as C5a, formylmethionyl‐leucyl‐phenylalanine (FMLP) and ionomycin, but MCP‐1 production was not induced by interleukin (IL)‐1 or tumor necrosis factor‐α. C5a‐ and FMLP‐induced eosinophil MCP‐1 production was absolutely dependent on pretreatment with cytochalasin B. Eosinophils elaborated significantly more MCP‐1 than neutrophils. Immunoreactive MCP‐1 was detected at 6 h of incubation with C5a or FMLP. Expression of MCP‐1 mRNA reached a maximum within the first 3 h after stimulation and then declined rapidly to a very low and stable level by 18 h. Pretreatment with IL‐5 markedly amplified C5a‐induced MCP‐1 production, and the enhancement occurred at the pretranslational level. Eosinophilactive chemokines such as eotaxin failed to induce MCP‐1 generation, even when eosinophils were primed by IL‐5. Since MCP‐1 exerts a potent histamine‐releasing effect on human basophils, our results indicate that eosinophils may regulate basophil mediator release with possible consequent contribution to the pathogenesis of allergic inflammation via a paracrine mechanism.
A DR17‐restricted T cell epitope from a secreted Mycobacterium tuberculosis antigen only binds to DR17 molecules at neutral pH
Authors: Geluk Annemieke , Van Meijgaarden Krista E. , De Vries Rene R. P. , Sette Alessandro , Ottenhoff Tom H. M. 
Published: March 2007

AbstractThe assembly of peptide‐major histocompatability class II complexes in vitro is accelerated at low pH, comparable to that found in the intracellular compartments of metabolically active antigen‐presenting cells (APC). Mycobacteria such as Mycobacterium tuberculosis reside in phagosomes with only mildly acidic pH. Therefore, we investigated the pH dependency of peptide‐HLA‐DR binding for several T cell epitopes of mycobacterial proteins, focussing particularly on well‐defined, immunodominant HLA‐DR17(3)‐restricted T cell epitopes: peptide (p) 3–13 from the cytoplasmic 65‐kDa heat shock protein of M. tuberculosis/M. leprae, and peptide 56–65 from the secreted 30/31‐kDa protein from M. tuberculosis/M. leprae. p3–13 bound to purified, cell‐free DR17 under both acidic and neutral conditions. Four other, unrelated DR17‐binding peptides showed the same pH‐dependent binding characteristics as p3–13. p56–65, however, only bound to purified DR17 at pH 7 but not at all at pH 4.5. These DR17 peptide binding data were confirmed in cell‐bound DR17, in T cell stimulation assays in which fixed APC were peptide‐pulsed at acidic or neutral pH before addition of peptide‐specific DR17‐restricted T cells. As far as we are aware, p56–65 is the only human T cell epitope binding to HLA exclusively at neutral pH. The binding characteristics of p56–65 may reflect dominant processing in alternative, less acidic vacuolar compartments specifically related to the generation of epitopes from (secreted) mycobacterial proteins. The observation that p56–65 is an immunodominant epitope for anti‐mycobacterial T cells suggests the relevance of such novel processing compartments in T cell‐mediated immunity.
Interleukin‐12 promotes a chronic intestinal nematode infection
Authors: Bancroft Allison J. , Else Kathryn J. , Sypek Joseph P. , Grencis Richard K. 
Published: March 2007

AbstractResistance and susceptibility to the intestinal parasite Trichuris muris has been shown to be due to a dominant T helper 2 (Th2) and a dominant Th1 response, respectively. The factors determining the initial polarization of the immune response remain largely unresolved, although the cytokine environment at the time of antigen presentation clearly plays an essential role. Interleukin (IL)‐12, a cytokine produced mainly by macrophages, dendritic cells, and other monocytes has been shown to be important in driving a strong Th1 response by stimulating the production of interferon (IFN)‐γ from natural killer and Th0 cells and therefore forms a link between the innate and adaptive immune system. IL‐12 has been shown to play an important role in resistance to a number of intracellular pathogens, including Listeria and Leishmania. It has also been proposed as an anti‐tumor agent and for use in the treatment of HIV. Conversely, IL‐12 has been shown to prolong the survival of Nippostrongylus brasiliensis and to accelerate autoimmunity. Our studies demonstrate that by driving a strong Th1 response, IL‐12 promotes chronic T. muris infection when given to normally resistant BALB/K mice. Parasite‐specific IgG2a, a Th1 parameter of infection, was greatly up‐regulated, whereas some Th2 parameters of infection were down‐regulated. IL‐12 treatment could be delayed until 1 week after infection had started and still promote a strong Th1 response. The actions of IL‐12 in promoting a chronic infection were IFN‐γ dependent as an anti‐IFN‐γ mAb abrogated the effects of IL‐12.
The Oka blood group antigen is a marker for the M6 leukocyte activation antigen, the human homolog of OX‐47 antigen, basigin and neurothelin, an immunoglobulin superfamily molecule that is widely expressed in human cells and tissues
Authors: Spring Frances A. , Holmes Christopher H. , Simpson Karen L. , Mawby William J. , Jules Mattes M. , Okubo Yasuto , Parsons Stephen F. 
Published: March 2007

AbstractThe high‐frequency blood group antigen Oka is carried on a red cell membrane glycoprotein (gp) of 35–69 kDa that is widely distributed on malignant cells of different origins. Immunostaining of hemopoietic cells and a range of normal human tissues demonstrated a wide distribution of the Oka gp that appears to be nonlineage‐restricted, although certain tissues show differentiation‐related expression. Oka gp was purified from red cell membranes by immunoaffinity chromatography using mAb A103 and amino acid sequence analysis was performed. The N‐terminal 30 amino acids are identical to the predicted sequence of M6 leukocyte activation antigen (M6), a member of the Ig superfamily (IgSF) with two IgSF domains. There are homologs in rat (MRC OX‐47 or CE9), in mouse (basigin or gp42), and in chicken (HT7 or neurothelin). The molecular basis of the Oka mutation was established by sequencing M6 cDNA derived from normal and Ok(a‐) EBV‐transformed B cell lines. A point mutation in the translated portion of M6 cDNA, G331 AG → AAG gives rise to a predicted E92 → K amino acid change in the first Ig‐like domain of the Ok(a‐) form of the protein. Transfection of mouse NS‐0 cells with normal or Ok(a‐) cDNA confirmed the identity of the protein and only the Ok(a‐) transfectants failed to react with monoclonal anti‐Oka Ab.
Comparative analysis of αβ and γδ T cell activation by Mycobacterium tuberculosis and isopentenyl pyrophosphate
Authors: Wesch Daniela , Marx Sibylle , Kabelitz Dieter 
Published: March 2007

AbstractPhosphorylated nonpeptide compounds have recently been identified as potent mycobacteria‐derived ligands for human Vγ9/Vδ2‐expressing γδ T cells. Crude mycobacterial extracts also contain protein antigens which stimulate CD4 αβ T cells to produce growth factors that are used by γδ T cells for clonal expansion. We have investigated the dynamics in vitro of expansion of CD4 T cells and Vγ9 cells in cultures of peripheral blood mononuclear cells stimulated with synthetic isopentenyl pyrophosphate (IPP) in the absence or presence of additional stimuli. The results indicated that following stimulation with IPP, γδ T cells express CD25 and CD69 antigens, but fail to proliferate unless growth factors are provided exogenously or endogenously through activation of CD4 T cells by additional stimuli such as tetanus toxoid, alloantigen, or superantigens. Furthermore, the presence of antigen presenting cells are required for expansion of γδ T cells. In response to IPP stimulation, purified CD4 T cells neither express CD25 or CD69, nor do they proliferate even in the presence of exogenous IL‐2. Apart from IL‐2, IL‐15 and, less efficiently, IL‐4, IL‐7, and IL‐12 can contribute to cellular expansion of IPP‐reactive Vγ9 cells. Together, the results demonstrate that peripheral blood γδ T cells proliferate in response to IPP only if CD4 T cells are simultaneously activated by an additional stimulus. This mechanism provides a tight control of the reactivity of γδ T cells towards phosphorylated nonpeptide antigens.
Role of ligands in the activation of LFA‐1
Authors: Buckley Christopher D. , Ferguson Elaine D. , Littler Amanda J. , Bossy David , Simmons David L. 
Published: March 2007

AbstractLymphocyte function‐associated‐antigen‐1 (LFA‐1) is able to bind selectively to its ligands intercellular adhesion molecules 1 and 3 (ICAM‐1 and ICAM‐3), suggesting that LFA‐1 can exist in distinct ligand‐specific binding states. In the case of ICAM‐1, apart from ligand itself and the recently cloned molecule cytohesin‐1, the natural physiological regulators of LFA‐1‐mediated binding to ICAM‐1 are unknown. We have investigated the role of ligands (ICAM‐1 and ICAM‐3) in LFA‐1 activation by using ICAM‐blocking monoclonal antibodies and a fixation protocol for “freezing” LFA‐1 on the surface of cells after prior exposure to ICAM‐1 and ICAM‐3. These studies not only confirm that LFA‐1 exists in distinct ICAM‐specific activation states, but also demonstrate that ICAM‐1 plays a role in the activation of LFA‐1 binding to ICAM‐3.
Differential generation of class I H‐2D‐ versus H‐2K‐restricted cytotoxicity against a demyelinating virus following central nervous system infection
Authors: Lin Xiaoqi , Pease Larry R. , Rodriguez Moses 
Published: March 2007

AbstractDespite the fact that both H‐2K and D molecules are up‐regulated in the central nervous system (CNS) following Theiler's murine encephalomyelitis virus (TMEV) infection, resistance in this virus model of multiple sclerosis maps exclusively to D. To address this paradox, we examined the ability of the K and D molecules to present viral antigens to cytotoxic T lymphocytes (CTL). Whereas no virus‐specific CTL were detected in the CNS of susceptible B10.Q and B10.S mice 7 days post‐infection, D‐restricted CTL were identified readily in the CNS of resistant B10 animals. There was no evidence of K‐restricted CTL in the CNS of B10 mice at day 7 post‐infection. The presence of both K‐ and D‐restricted virus‐specific CTL in the spleen of immunized B10 mice demonstrates that the exclusive use of D molecules by CTL in the CNS of mice 7 days post‐infection is not due to the inability of the K molecules to present viral peptides to lymphocytes. We conclude that the prominent role of the D locus in determining resistance or susceptibility to TMEV‐induced demyelination is determined by factors governing the regulation of the immune response, and not by the presence or absence of CTL precursors capable of recognizing viral peptides presented by the K and D antigen‐presenting molecules, or by differences in the ability of the K and D molecules to present viral peptides.
Engagement of the B lymphocyte antigen receptor induces presentation of intrinsic immunoglobulin peptides on major histocompatibility complex class II molecules
Authors: Bartnes Kristian , Hannestad Kristian 
Published: March 2007

AbstractBy means of the clonotypic variable region, the immunoglobulin (Ig) is a tumorspecific antigen on B cell neoplasms. We report that engagement of the B cell antigen receptor (BcR) promotes presentation of peptides derived from the B cell's intrinsic Ig to major histocompatibility complex (MHC) class II‐restricted T cells. Thus, anti‐Ig endowed normal, ex vivo B lymphocytes from H‐2d, Ig constant heavy chain allotype b (IgCHb) mice with the capacity to stimulate an I‐Ad‐restricted T cell clone which recognizes the γ2ab 435–451 allopeptide. The corresponding self γ2aa peptide is cryptic and 6000‐fold less antigenic than the γ2ab allopeptide. Even so, the syngeneic B cell lymphoma A20 which expresses surface (s) IgG2aa, was also recognized by the T cells after BcR ligation. Thus, anti‐Ig triggered the disclosure of a cryptic tumor antigen determinant. We propose that autoantigens, by engaging the BcR of self‐reactive B cells, induce presentation of intrinsic Ig peptides to which the T helper cell (Th) repertoire is not tolerant. In this way, B cells with anti‐self potential may be activated without Th recognition of nominal autoantigen.
Mimotopes of polyreactive anti‐DNA antibodies identified using phage‐display peptide libraries
Authors: Sibille Pierre , Ternynck Thérèse , Nato Faridabano , Buttin Gérard , Strosberg Donny , Avrameas Alexandre 
Published: March 2007

AbstractThree monoclonal IgG2a anti‐DNA polyreactive autoantibodies, derived from lupus‐prone mice (NZB X NZW)F1, were studied by surface plasmon resonance (BIAcore) analysis using three different synthetic double‐stranded (ds) oligonucleotides of 25, 30, and 25 base pairs (bp). These monoclonal antibodies (mAb) exhibited dissociation rate constants (koff) ranging from 0.0001 (mAb F14.6 and F4.1) to 0.01/s (mAb J20.8) and kon ranging from 2 × 105 to 2 × 106/M/s. The screening of a constrained random peptide library displayed on M13 bacteriophages on these mAb allowed the determination of the specific consensus motifs (mimotopes) for mAb F14.6 and J20.8, but not for mAb F4.1. No cross‐reaction was observed between F14.6‐ and J20.8‐specific peptides (and vice versa). Binding of all phages selected on F14.6 was inhibited with 700 ng/ml soluble DNA. The binding of one group of peptides selected on J20.8 was inhibited by 400 ng/ml soluble DNA, of a second group by 2500 ng/ml, while binding of a third group could not be inhibited. The determined consensus sequences do not match with known sequences. Peptides specific for F14.6 share negative charges and aromatic rings that may mimic a DNA backbone, while peptides selected with J20.8 do not bear any negative charge, implying a different kind of molecular recognition, for example hydrogen or salt bonds. The peptides selected on J20.8 also bind serum antibodies from human patients with systemic lupus erythematosus. In addition, BALB/c mice immunized with some of the selected phages exhibit high serum titers of IgG3 anti‐dsDNA antibodies, further supporting the hypothesis that peptide epitopes may mimic an oligonucleotide structure.
Analysis of the requirement for β2‐microglobulin for expression and formation of human CD1 antigens
Authors: Bauer Anton , Hüttinger Robert , Staffler Günther , Hansmann Cornelia , Schmidt Walter , Majdic Otto , Knapp Walter , Stockinger Hannes 
Published: March 2007

AbstractHuman CD1 form a group of nonpolymorphic leukocyte surface molecules with homology to major histocompatibility complex (MHC) proteins. Recent findings in human and in mouse demonstrate the capacity of CD1 molecules to present nonpeptide components like lipids or lipoglycans as well as peptides. We studied the involvement of β2‐microglobulin (β2m) in expression of the classic human CD1 proteins CD1a, CD1b, and CD1c. The β2m‐deficient human melanoma cell line FO‐1 was transiently transfected with either CD1a, CD1b, or CD1c DNA alone, or in combination with β2m using the adenovirus‐enhanced receptor‐mediated transfer infection system. Only co‐transfection of FO‐1 cells with CD1 + β2m resulted in the detection of CD1 Ag by monoclonal antibodies (mAb). This indicated that CD1 mAb recognized determinants are dependent on β2m and raised the question whether β2m‐free forms of CD1 can be expressed. Therefore, to visualize CD1 molecule expression independently of β2m, we expressed tagged recombinant forms. A full‐length CD1b construct tagged at the very C terminus with a small peptide was transported to the plasma membrane only when β2m was co‐transfected. β2m involvement in the transport of CD1 was confirmed by expression of soluble forms of CD1a, CD1b, and CD1c in three different cell types. Analogous to tagged full‐length CD1b, secretion of the soluble CD1 constructs was strictly dependent on β2m. The soluble CD1 chimeras were secreted as complexes with endogenous β2m. Thus, similar to its role for MHC class I expression, β2m is essential for processing and surface transport of the classic human CD1 molecules CD1a, CD1b, and CD1c.