bluuebunny/crossref_metadata_2025_split huggingface dataset:
A MEMBER OF A NEW VH GENE FAMILY ENCODES ANTI‐BROMELINIZED MOUSE RED BLOOD CELL AUTOANTIBODIES
Authors: Reininger Luc , Kaushik Azad , Izui Shozo , Jaton Jean‐Claude 
Published: March 2007

AbstractA cDNA clone encoding the variable region of the heavy chain of a BALB/c anti‐bromelinized mouse red blood cell (BrMRBC) monoclonal antibody has been characterized. The nucleic acid sequence indicates that the variable region of the heavy chain is likely encoded by variable‐VCP12, diversity‐DSP 2 (5, 7 or 8) and joining‐JH1 germ‐line genes. An identical combination of V genes was observed for six other CBA/J and NZB anti‐BrMRBC hybridomas. The BALB/c VCP12 nucleotide sequence is less than 80% homologous to members of the 10 known VH families. Moreover, the genomic restriction fragments detected under moderate stringency conditions with the radiolabeled cDNA probe did not correspond to those obtained with probes of the most homologous VH families (7183 and X24).The results indicate that the VCP12 gene defines a new VH family which we propose to designate vH11. The observation of 1, 2 or 3 enomic restriction fragments at the most, with mice bearing the Igh‐Vd or J, Igh‐Va or bF or Igh‐Vc haplotypes, suggests the existence of a few VCP12‐related genes.
Stable expression of the cDNA encoding the human T lymphocyte‐specific CD2 antigen in murine L cells
Authors: Clipstone Neil A. , Crumpton Michael J. 
Published: March 2007

AbstractThe human CD2 antigen is a T lymphocyte cell surface glycoprotein that has been implicated in both T lymphocyte adhesion and activation. The requirement for a T lymphocyte‐specific factor(s) in the mechanism of signal transduction initiated via the CD2 antigen has been explored using murine L cells transfectants that stably express the human CD2 antigen at the cell surface. Such transfectants express the three CD2 epitopes previously defined on human T lymphocytes. However, combinations of CD2 monoclonal antibodies, that stimulated an increase in the cytoplasmic calcium concentration of the human T cell line Jurkat, failed to induce a similar signal in the transfectants. These results indicate that the transfected CD2 antigen cannot alone transduce intracellular signals in response to stimulatory combinations of CD2 monoclonal antibodies, and suggest that the functional CD2 antigen expressed on human T lymphocytes requires the association of another, as yet undefined factor(s).
T‐immunogenic peptides are constituted of rare sequence patterns. Use in the identification of T epitopes in the human immunodeficiency virus gag protein
Authors: Claverie Jean‐Michel , Kourilsky Philippe , Langlade‐Demoyen Pierre , Chalufour‐Prochnicka Ada , Dadaglio Gilles , Tekaia Fredj , Plata Fernando , Bougueleret Lydie 
Published: March 2007

AbstractThe sequences of a set of 63 peptides of demonstrated T immunogenicity have been analyzed and compared with two different randomly generated sets of sequences. This study indicates a statistically significant tendency of T immunogenic peptides to be constituted of clusters of rare tetrapeptides, as evaluated from the available sequence data banks. This result has been used to locate potential T epitopes in the human immunodeficiency virus (HIV) gag protein. Four peptides corresponding to the best candidate T epitopes (chosen in regions of conserved sequence among different virus isolates) have been synthesized and found to be recognized by a HIV‐1‐specific, HLA‐A2‐restricted human cytotoxic T cell line.
T cell dependence of the “natural” autoreactive B cell activation in the spleen of normal mice
Authors: Huetz Fançois , Sciard‐Larsson Eva‐Lotta , Pereira Pablo , And Denis Portnoi , Coutinho Antönio 
Published: March 2007

AbstractA high frequency of clonal precursor B cells producing lytic antibodies to syngeneic erythrocytes treated with bromelain (BMRC) is revealed in normal mouse spleen cells by lipopolysaccharide‐driven limiting dilution analysis. All such specificities are recovered as activated blasts after density gradient fractionation, the “small lymphocyte” pool being depleted of anti‐BMRC reactivities. In contrast, the spleens of athymic (nude) mice contain undetectably low frequencies of these specificities in either lymphocyte compartment. Transfer of relatively low numbers of normal syngeneic splenic T lymphocytes to adult nude mice restores the high frequency of anti‐BMRC clonal precursor B cells, again in the activated, but not in the resting spleen cell fractions. Large total T cells are more than tenfold better than resting T cells in reconstitution potential, as are enriched CD4+ as compared to CD8+ cells which are practically devoid of activity in this respect. These results apply exclusively to B cells at a differentiative stage that allows for extensive clonal expansion, since there is a marked difference between the frequency of clonal precursors determined by limiting dilution analysis and the frequency of Ig‐secreting plaque‐forming cells of the same specificity, and induced by the same mitogen in short‐term cultures. The implications of these findings for the physiology of autoreactivity and repertoire selection in the compartment of perinatal B cells are discussed.
Highly efficient action of autocrine mouse interferon‐γ expressed via a retroviral vector
Authors: Watanabe Yoshihiko , Sakata Tsune‐Aki 
Published: March 2007

AbstractFollowing infection with a mouse interferon‐γ (IFN‐γ)‐producing retrovirus, various types of mouse cell lines began to constitutively secrete IFN‐γ in the culture medium, but the IFN‐γ production level varied according to cell type. Effects of the IFN‐γ on the IFN‐γ‐producing cell itself (autocrine effects) were examined. In the IFN‐γ‐producing cells, the expression of the major histocompatibility complex class I genes was augmented; this augmentation was remarkable in T cell lines tested in this work, regardless of their poor IFN‐γ production. This autocrine effect was highly efficient and could not easily be abrogated by the exogenous addition of anti‐IFN‐γ antibodies. Such antibody resistance was also observed for the antiviral effect of the autocrine IFN‐γ on an IFN‐γ gene‐transferred fibroblast line. These results suggest that apparently low titers of physiological IFN‐γ might exert strong in vivo autocrine and possibly paracrine effects.
Organization of the human CD3 locus on chromosome 11
Authors: Tunnacliffe Alan , Olsson Carina , Buluwela Lakjaya , Rabbitts Terence H. 
Published: March 2007

AbstractThree CD3 genes, γ, δ, ϵ map to human chromosome 11 band q23. A 75‐kb region of 11q23 containing all three genes has been characterized by field inversion gel electrophoresis and molecular cloning. The CD3 genes lie within a stretch of 50 kb of DNA, orientated 3′‐CD3γ‐5′:5′‐CD3δ‐3′ :3′‐CD3ϵ‐5′. Only 1.6 kb separate the CD3δ and CD3δ genes, while the CD3δ and CD3ϵ genes are approximately 22 kb apart. CD3 gene expression is one of the first events during the maturation of the thymocyte, and therefore the clustering of CD3 genes may define a chromatin domain which is activated early in T cell development.
Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation
Authors: Merkenschlager Matthias , Terry Linda , Edwards Robert , Beverley Peter C. L. 
Published: March 2007

AbstractUsing limiting dilution analysis, we investigated proliferative responses of UCHL1+ and UCHL1− T cell populations to compare the precursor cell frequencies following recall and alloantigen stimulation, and the complexity of cellular interactions within UCHL1+ and UCHL1− populations. We find high frequencies of recall antigen responses among UCHL l+, but not UCHL1− T cells. In contrast, both populations contain similar frequencies of alloantigen responsive cells. Our results are consistent with single‐hit kinetics in recall as well as alloantigen responses and show no complex cellular interactions within the responding populations. In conclusion, the difference between the recall antigen response of UCHL 1+ and UCHL1− cells observed in conventional proliferation assays is most probably due to a high frequency of recall antigen‐responsive UCHL1+ cells and not to suppressive phenomena in the UCHL1−population. These data suggest that memory T cells are largely of the UCHL 1+ phenotype. The relation of post‐thymic T cell maturation and differential CD45 expression is briefly discussed.
Regulatory effects of human IgE‐binding factors in the IgE synthesis by human and rat lymphocytes
Authors: Kisaki Tomonari , Leung Donald Y. M. , Jardieu Paula , Geha Raif S. , Ishizaka Kimishige 
Published: March 2007

AbstractWe have previously established human T cell hybridomas which produce IgE‐binding factors. Incubation of one of the T cell hybridomas, 166A2, with human IgE dimer in the presence of 1 μg/ml bradykinin resulted in the formation of IgE‐binding factors having affinity for lentil lectin. The factors selectively enhanced both IgE‐forming cell responses of rat mesenteric lymph node (MLN) cells and spontaneous IgE synthesis by human peripheral blood B cells of atopic patients, without affecting the IgG response. The same factors that enhanced IgE synthesis of B cells from atopic patients also enhanced IgE synthesis induced under bystander conditions by activated alloreactive T cells. Fractionation of the affinity‐purified IgE‐binding factors by gel filtration revealed three molecular mass species, i.e., 60 kDa, 30 kDa and 15 kDa. The 60‐kDa and 15‐kDa IgE‐binding factors selectively enhanced both the spontaneous IgE synthesis by B cells of atopic patients and IgE response of rat MLN cells. In contrast, the 30‐kDa IgE‐binding factors had only marginal enhancing effects on the IgE synthesis by both human B cells and rat MLN cells. When the 166142 hybridoma cells were incubated with IgE dimer in the presence of glycosylation‐inhibiting factor (GIF), essentially all IgE‐binding factors formed by the cells had affinity for peanut agglutinin (PNA) but for neither lentil lectin nor concanavalin A. All of the 60‐kDa, 30‐kDa and 15‐kDa species, having affinity for PNA, selectively suppressed the potentiating factor‐enhanced IgE response of rat MLN cells. The factors also suppressed the IgE synthesis of human B cells from atopic patients when the synthesis was enhanced by IgE‐potentiating factor. The results indicate that human IgE‐binding factors regulate IgE synthesis by both human and rat lymphocytes.
In vitro T cell responses to a candidate Epstein‐Barr virus vaccine: human CD4+ T cell clones specific for the major envelope glycoprotein gp340
Authors: Ulaeto David , Waace Lesley , Morgan Andrew , Morein Bror , Rickinson Alan B. 
Published: March 2007

AbstractSpecific T cell proliferation was observed in short‐term blood mononuclear cell cultures set up from Epstein‐Barr virus (EBV)‐immune individuals and challenged either with UV‐irradiated EB virions or with a candidate subunit vaccine preparation, the purified envelope glycoprotein gp340 incorporated into immune stimulating complexes (gp340 iscoms). Limiting dilution culture of the activated T lymphoblasts in interleukin 2‐containing medium generated stable CD3+CD4+CD8‐ T cell clones. Particular clones showing virus‐specific proliferation in preliminary screening assays were selected for more detailed study. Three gp340 iscoms‐induced clones from EBV‐immune donor CG responded specifically to restimulation either with UV‐EBV or with purified gp340 iscoms in the presence of autologous antigen‐presenting cells (APC). Both T cell‐depleted blood mononuclear cells and the EBV‐transformed B cell line (treated with Acyclovir to block endogenous gp340 production) could be used for presentation, the latter being the more efficient when gp340 iscoms was the source of antigen. Blocking studies with monoclonal antibodies to HLA class II antigens and experiments using HLA‐typed allogeneic APC indicated that all three gp340‐specific CG clones were restricted through the HLA‐DR2 antigen. One gp340 iscoms‐induced clone from another EBV‐immune donor, MR, likewise showed gp340‐specific proliferation, in this case restricted through a HLA‐DR4 antigen. Using HLA‐DR‐homozygous B cell lines representing the five known DR4 subtypes, efficient presentation of gp340 to this T cell clone was observed with both DR4Dw4 and DR4Dw14 antigens. Parallel experiments on one UV‐EBV‐induced T cell clone from donor MR gave a different pattern of results; these cells appeared to be specific for a virus structural component other than gp340 and to be restricted through an HLA‐DP determinant.
Complement activation is not required for IgG‐mediated suppression of the antibody response
Authors: Heyman Birgitta , Wiersma Erik , Nose Masato 
Published: March 2007

AbstractFeedback suppression of the antibody response by IgG is known to be dependent on intact Fc regions. However, it is not clear which of the Fc‐mediated effector functions is required. In the present report we have studied whether ability or inability of the IgG antibodies to activate the complement system was of consequence for their immunosuppressive effectFirst, a monoclonal IgG1‐anti‐2,4,6‐trinitrophenyl (TNP) antibody, unable to activate complement via the classical or alternate pathway, was shown to be able to inhibit more than 90% of the in vivo sheep erythrocyte‐specific antibody response in mice when TNP coupled to sheep erythrocytes was used as antigenSecond, we investigated the immunosuppressive ability of a non‐complement‐activating mutant IgG2a,‐anti‐TNP monoclonal antibody. The mutant differs from the wild type by a single amino acid substitution in the CH2 domain leading to inability to fix complement factor Clq. However, the mutant has the same affinity for antigen and the same Fc receptor‐binding capacity as the wild type antibody. It is demonstratd that the mutant was as efficient as the wild type antibody in inhibiting an in vitro antibody response to TNP‐coupled sheep erythrocytesThese findings confirm the non‐determinant specificity and Fc dependence of IgG‐mediated suppression, and show that the Fc‐mediated effector mechanism is independent of complement activation. The results instead suggest binding to Fc receptors as a necessary step in feedback immunosuppression and favor inactivation of B cells by cross‐linking of Fc and antigen receptors on their surface rather than elimination of antigen by complement‐dependent phagocytosis as the effector mechanism.
Establishment of tumor‐specific immunotherapy model utilizing vaccinia virus‐reactive helper T cell activity
Authors: Shimizu Yoshio , Hasumi Katsuhiko , Masubuchi Kazumasa , Okudaira Yoshio 
Published: March 2007

AbstractIt was previously demonstrated that preimmunization of mice with live vaccinia virus (VV) and subsequent immunization with VV‐infected (modified), syngeneic tumor cells resulted in enhanced induction of tumor‐specific immunity through a cellular collaboration between VV‐reactive helper T (VV‐Th) cells and tumor‐specific effector cell precursors. On the basis of this augmenting system, a tumor‐specific immunotherapy model was established in which a growing tumor regressed.C3H/HeN mice were pretreated with cyclophosphamide to eliminate nonspecific suppressor T cell activity and subsequently inoculated (primed) s.c. with live VV, leading to augmented induction of VV‐Th cell activities. Four weeks later, the mice were inoculated i.d. with syngeneic X5563 myeloma cells. Six days after the tumor cell inoculation, live VV was injected into the tumor mass three times at 2‐day intervals. Seven of ten mice which had received VV priming and subsequent VV injection into the tumor mass exhibited complete tumor regression. On the contrary, mice which had received mere intratumoral VV injection in the absence of VV priming failed to exhibit appreciable tumor regression. Mice whose tumor had completely regressed (regressor mice) by the above VV immunotherapy were shown to have acquired systemic anti‐tumor immunity, which was confirmed by a challenge with syngeneic tumor cells after the tumor regression. In vitro analysis of these immune mice revealed that potent tumor‐specific cytotoxic T lymphocyte responses were preferentially induced, but with no detectable anti‐tumor antibody responses. Such a potent tumor‐specific immunity was not observed in mice which had received an intratumoral VV injection in the absence of VV priming. Thus the results clearly indicate that the tumor regression was accompanied by concurrent generation of a potent tumor‐specific immunity, suggesting that the cellular collaboration between VV‐Th cells and tumor‐specific effector cell precursors is also functioning in this VV‐immunotherapy protocol, likewise the immunoprophylactic model. Therefore, the present model provides an effective maneuver for tumor‐specific immunotherapy and this system will be theoretically applicable to human cancer treatment.
Age‐associated increase in the expression of T cell antigen receptor γ chain genes in mice
Authors: Matsuzaki Goro , Yoshikai Yasunobu , Kishihara Kenji , Nomoto Koji , Yokokura Teruo , Nomoto Kikuo 
Published: March 2007

AbstractT cell function generally declines with age. To determine the underlying cause of the age‐related decline, we compared the expression levels of T cell antigen receptor genes encoding γ, β and α chains in the lymphoid tissues of young (8 wk old) vs. aged (40 wk old) mice. An age‐associated increase in γ chain gene transcripts was evident in the thymocytes, spleen cells and mesenteric lymph node cells. Aged mice had a relatively high proportion of CD3+CD4−CD8− cells but a reduced level of CD3+CD4−CD8+ cells in the lymphoid tissues, as compared with young counterparts. The allo‐reactivity in the lymphoid cells, as assessed by mixed lymphocyte reaction (MLR) responses, decreased with advancing age. On the contrary, increased levels of syngeneic MLR and spontaneous cytolytic activity were noted in the lymphoid cells of aged mice, as compared with findings in their young counterparts. A remarkable increase in the number of CD3+CD4−CD8− cells and level of the γ chain gene messages was also detected in the responder cells of day 4 syngeneic MLR culture from aged mice. An increase in the number of T cells bearing γ chain may be related to the alterations in immunological functions in aged mice.
Prostaglandin E2 and the increase of intracellular cAMP inhibit the expression of interleukin 2 receptors in human T cells
Authors: Rincón Mercedes , Tugores Antonio , López‐Rivas Abelardo , Silva Augusto , Alonso Miguel , De Landázuri Manuel O. , López‐Botet Miguel 
Published: March 2007

AbstractWe have analyzed the effect mediated by prostaglandin E2 (PGE2) and different reagents that increase intracellular cAMP on the expression of the p55 subunit (CD25) of interleukin 2 receptors (IL2R), on the levels of CD25‐specific mRNA and on the expression of high affinity IL 2R. In purified T cells, activated either by an anti‐CD3 monoclonal antibody or phytohemagglutinin, the addition of PGE2 (10−6 M), forskolin (5 × 10−5 M), cholera toxin (0.2 μg/ml) or dibutyryl cAMP (dBcAMP) (10−4 M) decreased the cell surface expression of IL 2R by reducing (40%‐78% inhibition) the proportions of CD25+ cells as well as the expression of high affinity IL2R, detectable after 24 h. Furthermore, it was observed that PGE2 reduced the concentration of IL2R‐specific mRNA after a 6‐h period of activation, indicating that its regulatory activity takes place at a pretranslational level. The addition of exogenous recombinant IL2 only partially reversed the inhibition, thus suggesting that PGE2 and increased intracellular concentration of cAMP directly interfered with CD25 expression and that their effect could not be merely attributed to a lack of IL2 dependent positive feedback. Cells cultured under the same conditions in the presence of phorbol myristate acetate, that activates protein kinase C, were refractory to the CAMP‐mediated regulation. Finally, we demonstrate that both PGE2 and dBcAMP inhibit the generation of inositol metabolites after T cell activation, thus indicating that these reagents interfere with early signal transduction mechanisms which precede the synthesis of IL2R.
PB76: a novel surface glycoprotein preferentially expressed on mouse pre‐B cells and plasma cells detected by the monoclonal antibody G‐52
Authors: Strasser Andreas 
Published: March 2007

AbstractA monoclonal antibody (mAb) G‐5‐2 was isolated which binds to transformed as well as normal cells of the B lineage but not to cells of the T cell, myeloid lineages nor to fibroblasts. mAb G‐5‐2 reacts with pre‐B and plasma cell‐transformed lines, and it preferentially recognizes normal pre‐B cells from fetal liver and bone marrow as well as plasma cells from spleen of mice. G‐5‐2+ fetal liver cells isolated by cell sorter express mRNA for μ heavy chain Ig gene and generate in vitro antibody‐producing cells when co‐cultured with lipopolysaccharide and rat thymocyte filler cells. During development the frequency and staining intensity of G‐5‐2+ cells in fetal liver from normal mice increases from 1% G‐5‐2+ cells at day 14 to∼7% positive cells at day 18 of gestation. Several strains or normal mice contain comparable numbers of G‐5‐2+ cells as well as B‐220+ and BP‐1+ B cell precursors in the fetal liver. Mice carrying the xid mutation have 3‐4‐fold less G‐5‐2+ as well as B‐220+ and BP‐1+ cells in the fetal liver, suggesting that the effects of the xid mutation may be manifested from early stages of B cell development. Fetal liver cells from mice carrying the scid mutation were found to contain normal numbers of G‐5‐2+ as well as B‐220+ and BP‐1+ pre‐B cells. These results indicate that differentiation from progenitors to pre‐B cells in scid mice may occur normally; the scid mutation would thus appear to affect the process of rearrangement and expression of the Ig genes in the developing pre‐B cells. mAb G‐5‐2 precipitates a 76‐kDa glycoprotein from surface‐radiolabeled pre‐B cells and plasma cells. Taken together, these results indicate that G‐5‐2 mAb recognizes a novel B cell lineage‐specific surface molecule called PB76 which is preferentially expressed by pre‐B cells and plasma cells.
T cell responses of normal individuals towards recombinant protein antigens of Mycobacterium tuberculosis
Authors: Munk Martin E. , Schoel Bernd , Kaufmann Stefan H. E. 
Published: March 2007

AbstractRecombinant β‐galactosidase fusion proteins from Mycobacterium tuberculosis were purified by affinity chromatography and used for stimulation of unselected T lymphocytes freshly isolated from healthy individuals. It was found that the 12kDa, 19‐kDa, 65‐kDa and 71‐kDa recombinant (r) proteins tested stimulated T cells from healthy individuals in an antigen‐specific way. These data demonstrate that it is feasible to screen purified r‐proteins with unselected T cell populations. The existence of T cells with reactivity to these antigens in healthy individuals suggests T cell activation independent from clinical disease and hence that these proteins are not indicative for active tuberculosis.
A VH gene is located within 95 Kb of the human immunoglobulin heavy chain constant region genes
Authors: Buluwela Lakjaya , Rabbitts Terence H. 
Published: March 2007

AbstractUsing cosmids covering about 117 Kb upstream of the human immunoglobulin chain C, gene, we have identified a potentially functional VH gene, belonging to the VHVI subgroup. This VHVI gene is only about 95 Kb from the Cμ gene and is probably the first functional VH segment of the Igh locus. These results illustrate the proximity of the human VH, DH and JH segments involved in creation of the complete heavy chain genes.