bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genesis of host IgE competence: perinatal IgE tolerance induced by IgE processed and presented by IgE Fc receptor (CD23)‐bearing B cells
Authors: Chen Swey‐Shen Alex 
Published: March 2007

AbstractA murine model for studying life‐long IgE tolerance was previously developed in this laboratory by perinatal IgE injection into neonates. Herein, we demonstrated that normal and immortal CD23+ B cell lines presented processed IgE via CD23‐mediated endocytic pathway and triggered perinatal IgE tolerance. The observations were as followed: (a) CD23 on normal B cells or B cell hybridomas mediated IgE‐dependent perinatal IgE tolerance and total IgE deficiency; and lack of either antigen‐specific IgE or total IgE did not correlate with elevated levels of autologous anti‐IgE in individual mice; (b) IgE tolerance‐inducing capacity of CD23+ B cell hybridomas was augmented by treatment with antigen‐IgE complexes orinterleukin 4, and significantly inhibited by anti‐CD23 prior to IgE pulsing; (c) antigen‐IgE complexes were endocytosed and degraded in acid hydrolases‐containing vesicles; and IgE tolerance was abrogated by treating IgE‐pulsed 17A11 at 4°C or 20°C followed immediately by fixation, and by treating IgE‐pulsed 17A11 with metabolic inhibitors that elevated intracellular pH of the endocytic vesicles. In conclusion, this study suggested that one pivotal step of genetic control of IgE responses may be exercised at the early developmental stage of T cells of the IgE lineage, and that CD23 may facilitate capture of endogenously secreted IgE, and mediate endocytic processing and presentation of self IgE epitope(s), and thus contribute to the genesis of host IgE competence.
Regulated expression on human macrophages of endoglin, an Arg‐Gly‐Asp‐containing surface antigen
Authors: Lastres Pedro , Bellon Teresa , Cabañas Carlos , Sanchez‐Madrid Francisco , Acevedo Agustin , Gougos Anne , Letarte Michelle , Bernabeu Carmelo 
Published: March 2007

AbstractEndoglin is an endothelial homodimeric membrane antigen containing the tripeptide arginine‐glycine‐aspartic acid (RGD), which is a recognition motif for adhesion receptors of the integrin family. We have investigated the expression of endoglin by monocyte/macrophage cells from different tissue compartments and at different stages of cell differentiation. Although endoglin is absent from peripheral blood monocytes, it is expressed by in vitro differentiated monocytes as determined by flow cytometry using the endoglin‐specific monoclonal antibody 44G4 and 8E11. Furthermore, Northern blot analyses revealed a correlation between the presence of endoglin mRNA and the surface expression of the antigen by in vitro differentiated monocytes. Immunostaining of frozen tissue sections with the 8E11 monoclonal antibody demonstrated the presence of endoglin not only in the endothelium of all the tissues studied, but also on the interstitial macrophages present in the red pulp of the spleen. Using as a model of macrophage differentiation monocytic cell lines treated with phorbol esters, we found that the reactivity of the 8E11 monoclonal antibody is greatly increased on U‐937 and HL‐60 cells during their PMA‐induced differentiation. These findings clearly demonstrate for the first time the regulated expression of the putative adhesion molecule endoglin by macrophages.
Homologous collagen‐induced arthritis in ratg and mice are associated with structurally different major histocompatibility complex DQ‐like molecules
Authors: Holmdahl Rikard , Vingsbo Carina , Hedrich Hans , Karlsson Mikael , Kvick Christina , Goldschmidt Tom J. , Gustafsson Kenth 
Published: March 2007

AbstractCollagen‐induced arthritis (CIA) in rats, induced with homologous type II collagen (CII), is a genetically more restricted disease and has better resemblance to rheumatoid arthritis by its chronic disease course, than CIA induced with heterologous CII. The DA strain is highly susceptible to CIA induced with homologous CII, while the Lewis strain is resistant. (DAxLew)F1 is susceptible and backcrossing to Lewis reveals a close, but not complete, association of both arthritis and CII responsiveness to the RT1a haplotype. Analyses of congenic strains on DA and Lewis backgrounds suggest that expression of a major histocompatibility complex class II Ba molecule, encoded from the RT1Ba locus, is associated with arthritis susceptibility and CII responsiveness. The second exons coding for the first domains of the α and β chains of both the RT1a and RT11 haplotypes were sequenced and the deduced amino acid sequences compared with the corresponding molecule associated with susceptibility to CIA in the mouse (H‐2 Aq). The sequences of the respective alleles revealed no obvious structural homology explaining the extensive similarities in the development of chronic autoimmune arthritis. Instead, this finding implies that different trimolecular constituents (i.e. class II,T cell receptor, and CII peptides) may yield an antigen presentation event that is able to trigger a similar autoaggressiveness in the two rodent species.
The CD27 membrane receptor, a lymphocyte‐specific member of the nerve growth factor receptor family, gives rise to a soluble form by protein processing that does not involve receptor endocytosis
Authors: Loenen Wil A. M. , de Vries Evert , Gravestein Loes A. , Hintzen Rogier Q. , Van Lier René A. W. , Borst Jannie 
Published: March 2007

AbstractCD27 is a transmembrane glycoprotein found exclusively on human T and B lymphocytes. It belongs to a recently identified receptor family, whose members are involved in cell differentiation and survival. This family includes the nerve growth factor receptor, two different types of tumor necrosis factor, receptors the Fas antigen, and the B cell‐specific protein CD40. T cell activation via the antigen receptor strongly enhances CD27 membrane expression, suggesting a role for CD27 during T cell differentiation. A soluble form of CD27 (sCD27) is released into the supernatant of activated T cells, and detected in serum and urine of healthy individuals and patients.We have investigated the mechanism underlying the generation of sCD27. One mRNA encodes both the transmembrane receptor and sCD27, as shown by cDNA transfection. In line with this, only one CD27 precursor protein is found, that is processed to the mature receptor by extensive O‐linked glycosylation. All newly synthesized protein is rapidly transported to the plasma membrane; no internal pool of mature protein is detectable. The transmembrane form gives rise to sCD27 after arrival at the cell surface, most likely via a proteolytic event, that does not involve receptor internalization.
Glycosylation of CD45: carbohydrate processing through Golgi apparatus is required for cell surface expression and protein stability
Authors: Pulido Rafael , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractThe importance of glycosylation on cell surface expression, protein stability and function of the CD45 phosphotyrosine phosphatase leukocyte common antigen, has been studied in the K562 erythroleukemic cell line. Cell treatment with the N‐glycosylation inhibitor tunicamycin generated unglycosylated CD45 polypeptides of 130 and 140 kDa. Immunofluorescence flow cytometry and Scatchard techniques revealed that CD45 cell surface expression was decreased in a time‐and dose‐dependent manner upon tunicamycin incubation. Moreover, a remarkable decrease in CD45 phosphatase activity was detected in tunicamycin‐treated cells, which correlated with the diminished CD45 cell surface expression. Pulse‐chase biosynthetic assays demonstrated that the fate of the unglycosylated CD45 proteins underwent a late non‐lysosomal degradation, since it was not prevented either by monensin, an inhibitor of Golgi transport, or by the lysosomal function inhibitor chloroquine. These results demonstrate that intact glycosylation of CD45 molecules through Golgi compartment is required for stability and proper transport towards the plasma membrane of these phosphotyrosine phosphatase proteins.
Characterization of the bovine peripheral lymph node homing receptor: a lectin cell adhesion molecule (LECAM)
Authors: Walcheck Bruce , White Michael , Kurk Sandy , Kishimoto Takashi K. , Jutila Mark A. 
Published: March 2007

AbstractThe phenomenon of tissue‐specific homing of lymphocyte populations has been most clearly shown in larger domestic animals, such as the sheep and cow, yet the molecular interactions which control these processes in these animals have not been defined. Here we tested the cross‐reactivity of four anti‐human peripheral lymph node homing receptor (LECAM‐1) (also known as LAM‐1, LEC‐CAM‐1, Leu‐8, TQ‐1, or human equivalent of gp90 MEL‐14) antibodies on bovine lymphocytes. These antibodies stained all bovine neutrophils and monocytes, and variable numbers of peripheral blood lymphocytes, as determined by flow cytometry. In young calves (< 1 month old) virtually all circulating lymphocytes expressed LECAM‐1, whereas the percentage of positive lymphocytes in older animals (> 1 year) varied from 17%–67%. Bovine LECAM‐1 was rapidly lost from the cell surface of PMA‐activated and chymotrypsin‐treated cells. Anti‐LECAM‐1 monoclonal antibody blocked > 80% of bovine lymphocyte binding to peripheral lymph node high endothelial venules (HEV). Since the lectin domain of LECAM‐1 is thought to mediate lymphocyte‐HEV adhesion, we sought to establish further the similarity of the bovine, mouse, and human molecules by comparing nucleotide sequences in this region of the molecule. The polymerase chain reaction (PCR) was used to specifically clone the bovine lectin domain from single‐strand cDNA. Subsequent sequencing showed an identity of >80% at the nucleotide level with the human and mouse molecules. The predicted amino acid sequences were also highly conserved. Though striking similarities were seen between the bovine, mouse and human molecule, indicating evolutionary conservation of this family of proteins, notable differences were detected. The nucleotide sequence of the bovine lectin domain predicts one additional N‐linked glycosylation site compared to mouse and human. Preliminary analysis suggested a more tissue‐restricted expression of LECAM‐1 in the compared to the human and mouse, which correlates with a better separation of lymphocyte homing phenotypes seen in these larger animals. Virtually all peripheral lymph node lymphocytes in 6‐month‐old calves expressed LECAM‐1, whereas, ileal Peyer's patch lymphocytes were predominantly negative. Finally, by testing anti‐human LECAM‐1 antibodies in a different species we have established the co‐expression of antigenic epitopes on leucocyte LECAM‐1 and a molecule(s) expressed by endothelial cells.
Superior cross‐protective effect of nasal vaccination to subcutaneous inoculation with influenza hemagglutinin vaccine
Authors: Tamura Shin‐Ichi , Asanuma Hideki , Ito Yuji , Hirabayashi Yoshihiro , Suzuki Yujiro , Nagamine Takashi , Aizawa Chikara , Kurata Takeshi , Oya Akira 
Published: March 2007

AbstractIntranasal (i.n.) vs. subcutaneous (s.c.) administration of influenza hemagglutinin (HA) vaccine was systematically compared in BALB/c mice. Mice were immunized with different vaccines, together with cholera toxin B subunit as an adjuvant, and 4 weeks later were challenged with either a small (2 μl) or a large (20 μl) volume of mouse‐adapted A/Guizhou‐X (H3N2) virus, each of which gave virgin mice either a nasal or a lung predominant infection. Both i.n. and s.c. inoculations of A/Guizhou‐X vaccine conferred almost complete protection against both challenges. i.n. inoculation of A/Fukuoka (H3N2) or A/Sichuan (H3N2) vaccine conferred almost complete cross‐protection against 2‐μl challenge and a partial cross‐protection against 20‐μl challenge, whereas the s.c. inoculation conferred no cross‐protection against 2‐μl challenge with a partial cross‐protection against 20‐μl challenge. Moreover, i.n. immunization of PR8 (H1N1) vaccine gave a slight cross‐protection against 2‐μl challenge, while the s.c. inoculation did not. The degree of protection was easily improved by i.n. inoculation of higher doses of vaccine, but not by the s.c. inoculation. In parallel with the protection, the i.n. vaccination produced a high level of cross‐reacting IgA and IgG antibody to A/Guizhou‐X HA in nasal and broncho‐alveolar washes, while the s.c. vaccination produced the cross‐reacting IgG antibody alone. Thus, i.n. inoculation with inactivated vaccines, which induces crossreacting anti‐HA IgA antibody as well as IgG antibody, is more effective than s.c. vaccination for providing cross‐protection against drift viruses.
Mouse autoreactive γ/δ T cells II. Molecular characterization of the T cell receptor
Authors: Ezquerra Angel , Wilde David B. , McConnell Thomas J. , Sturmhöfel Knut , Valas Robert B. , Shevach Ethan M. , Coligan John E. 
Published: March 2007

AbstractA panel of dendritic epidermal T cell (DETC) lines, and hybridomas derived from them, has been shown to spontaneously secrete lymphokines in the absence of added stimuli, which suggests that these cells are autoreactive. These cell lines are characterized by the expression of a Vγ1.1Cγ4/Vδ6 type T cell receptor (TcR), but several of the DETC lines also express a second TcR. Sequence analyses of these γ/δ TcR revealed that the γ chains were identical and that the δ chains, while not identical, were quite restricted in diversity, indicating that these receptors may recognize a common or closely related group of antigens. Analysis of hybridomas derived from newborn thymocytes identified six hybridomas that spontaneously secrete lymphokines. Five hybrids expressed a Vγ1.1Cγ4/Vδ6 receptor and one hybrid a Vγ1.1Cγ4/Vδ4 receptor that had a close structural relationship to the DETC γ/δ TcR associated with spontaneous lymphokine secretion. γ/δ TcR of the Cγ4 type expressed by splenic hybridomas that did not spontaneously secrete lymphokines revealed no such relationship. Curiously, like the DETC, several of the thymocyte hybridomas that spontaneously secreted lymphokines expressed a second TcR, Vγ2Cγ1 or Vγ3Cγ1, apparently in association with the same δ chain that paired with the Cγ4 chain. The presence of spontaneous lymphokinesecreting γ/δ T cells with such highly homologous TcR in both the thymus and skin suggests a thymic origin for the autoreactive DETC and that these cells recognize a common or closely related group of self‐antigens.
Regulation of immunoglobulin gene expression in normal lymphocytes II. Mechanisms of down‐regulation of immunoglobulin secretion after engagement of the B cell antigen receptor
Authors: Berberich Ingolf , Schimpl Anneliese 
Published: March 2007

AbstractWhen B cells are stimulated with lipopolysaccharide (LPS) they start to proliferate and mature into immunoglobulin (Ig)‐secreting cells. Co‐stimulation with F(ab')2 fragments of antibodies directed against the B cell antigen receptor leads to an inhibition of Ig secretion but not of proliferation. This effect can be mimicked by phorbol esters alone or by a combination of phorbol esters and the Ca2+ ionophore ionomycin, which activate protein kinase C. Here we report that co‐stimulation with phorbol esters and ionomycin differentially affects a group of genes normally up‐regulated during the course of LPS‐dependent B cell activation. Thus, the mRNA coding for the membrane‐bound form of IgM and the interleukin 2 receptor (55‐kDa protein) continue to be expressed at the levels typical of LPS‐stimulated cells, while the mRNA coding for the secreted form of IgM (μs) and for the J chain are reduced. The loss of μS mRNA is attributable to an altered processing behavior with respect to the μ precursor and/or a decreased stability of the mRNA itself.
Variation in human T cell receptor Vβ and Jβ repertoire: analysis using anchor polymerase chain reaction
Authors: Rosenberg William M. C. , Moss Paul A. H. , Bell John I. 
Published: March 2007

AbstractAnchor polymerase chain reaction has been applied to the study of human T cell receptor β chain repertoire in peripheral blood. The use of this technique has demonstrated that considerable variation in Vβ and Jβ usage exists, both within and between individuals. Particular Vβ families, including Vβ6, Vβ4 and Vβ12 are commonly utilized, while families such as Vβ10, Vβ11 and Vβ15 are rare in all individuals studied. Marked interindividual variation in Vβ usage was detected for Vβ12 and Vβ4. Biased usage of Jβ elements is a prominent feature of peripheral repertoire, while there is no evidence for preferential Vβ‐Jβ recombination events. Biased Jβ usage in expressed Vβ‐Dβ‐Jβ‐Cβ transcripts, subject to selection, was the same as that in aberrant, unselected Dβ‐Jβ‐Cβ transcripts, implying that bias resulted from events relating to rearrangement itself, in the absence of selection. N‐region diversity showed some evidence for preferential insertion of deoxyguanosine, consistent with the action of terminal deoxytransferase. No P‐nucleotide incorporation was seen in association with intact Jβ elements. These data provide evidence of some of the variation in human T cell receptor β chain repertoire and provide a basis for comparisons with sequences which may be obtained in autoimmune and superantigen‐mediated diseases.
Selective reactivity of CD8‐independent T lymphocytes to a cytotoxic T lymphocyte‐selected H‐2Kb mutant altered at position 222 in the α3 domain
Authors: Shepherd Sara E. , Sun Rui , Nathenson Stanley G. , Sheil James M. 
Published: March 2007

AbstractTo study the structural basis for specificity and affinity of cytotoxic T lymphocytes for major histocompatibility complex/peptide complexes, we have employed a cytotoxic T lymphocyte (CTL)‐mediated immunoselection approach to obtain H‐2Kb structural mutants which are resistant to lysis by a Kb‐specific alloreactive CTL clone. In this study we describe the Kb structural mutant, designated R8.60.14, recovered following immunoselection using the CD8‐dependent CTL clone 60 as a selective agent. Although serologically unaltered with respect to Kb expression, R8.60.14 is not recognized by CD8‐dependent, Kb‐specific CTL. DNA sequence analysis revealed a single Glu → Lys amino acid substitution at position 222 in the Kb α3 domain of this variant. To determine if a direct correlation exists between CD8 dependence of a Kb specific CTL and its failure to respond to R8.60.14, we examined the lytic response against R8.60.14 by CD8‐independent, Kb‐specific CTL obtained from long‐term culture in the presence of anti‐CD8 monoclonal antibody, 3.155. CD8‐independent CTL exhibit no difference in their response against the R8 parent and R8.60.14 variant. This study demonstrates unequivocally that Kb‐specific recognition of R8.60.14 by CD8‐independent CTL is unaltered, while the response by CD8‐dependent CTL is completely abrogated. Thus, the sole basis for emergence of this variant in the CTL‐mediated immunoselection approach used in this study resides in the alteration of a single CD8‐binding site residue at position 222 in the Kb α3 domain. The functional importance of this Glu222 residue for the interaction between the CD8 molecule on CD8‐dependent CTL and the Kb α3 domain is further reinforced by virtue of the recovery of the R8.60.14 variant on the basis of its resistance to lysis by a CD8‐dependent CTL clone in this CTL‐mediated immunoselection approach.
Interaction of CD4:lck with the T cell receptor/CD3 complex induces early signaling events in the absence of CD45 tyrosine phosphatase
Authors: Deans Julie P. , Kanner Steven B. , Torres Raul M. , Ledbetter Jeffrey A. 
Published: March 2007

AbstractAntibody‐mediated ligation of the CD3/T cell antigen receptor (TcR) activates phospholipase C (PLC) via a tyrosine kinase signaling pathway that requires expression of the transmembrane tyrosine phosphatase CD45. In normal T cells, CD3‐mediated PLC activation is significantly augmented by co‐ligation of CD3 with the CD4 co‐receptor; however, unlike CD3‐associated tyrosine kinases, antibody‐induced activation of the CD4‐associated tyrosine kinase p56lck does not require CD45 expression. To explore the role of CD45 in the CD3 and CD4 activation pathways further, we examined the effect of CD3/CD4 cross‐linking on tyrosine phosphorylation and activation of phospholipase C in CD45− mutant cells of the T cell leukemia line HPB.ALL. In accord with previous observations, anti‐CD3 stimulation of the CD45‐deficient cells failed to activate tyrosine kinases, or PLC as measured by mobilization of intracellular calcium. However, we show here that ligation of CD3 with CD4 leads to tyrosine phosphorylation of PLCγ1 and elevation in the intracellular free Ca2+ concentration in CD45− cells that is in excess of that seen in CD45+ cells. Since CD4 stimulation alone did not activate PLC, a component of the CD3 signaling pathway must be independent of CD45. Anti‐CD4‐induced tyrosine phosphorylation and activation of CD4‐associated lck was also enhanced in CD45− cells, suggesting that increased lck activation compensates for the defect in CD3/TcR signaling, such that interaction of the CD3 signaling pathway with the CD4‐associated pathway activates PLC even in the absence of CD45. The data demonstrate that the requirement for CD45 in coupling CD3/TcR to the PI‐PLC activation cascade is not absolute, but rather substantiates a role for CD45 in modifying molecular interactions that control T cell activation.
Weak positive selection of transgenic T cell receptor‐bearing thymocytes: importance of major histocompatibility complex class II, T cell receptor and CD4 surface molecule densities
Authors: Bogen Bjarne , Gleditsch Lars , Weiss Siegfried , Dembič Zlatko 
Published: March 2007

AbstractWe have produced αβ T cell receptor (TcR)‐transgenic mice and studied MHC‐dependent positive selection of T cells bearing this receptor. The α and β transgenes were isolated from an I‐Ed‐restricted, CD4+ BALB/c (H‐2d/d) T cell clone specific for a peptide consisting of the 91–101 residues of the λ2 immunoglobulin light chain of MOPC315. Mice which carry the transgenes on a BALB/c background, but with H‐2d/d, H‐2b/d or H‐2b/b major histocompatibility complex (MHC) haplotypes, were investigated for TcR expression in thymocytes and peripheral T cells. The thymocytes expressing the transgene‐encoded αβ receptor are weakly positively selected when compared with previous findings in other TcR‐transgenic mice models. Thus, αβ thymocytes vary in their efficacy of being positively selected by their restriction element. Furthermore, the density of TcR and CD4 on thymocytes, as well as the density of I‐Ed molecules on thymic epithelial cells, appear critical for the extent of positive selection. A possible explanation is that the transgenic TcR has a marginal affinity for self‐MHC molecules on thymic epithelium, and that this may be compensated for by an increase in the number of CD4/TcR/MHC ternary complexes forming between the maturing thymocyte and the cortical epithelial cells.