bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative T cell receptor gene usage induced by self tolerance
Authors: Frangoulis Bernard , Pla Marika , Rammensee Hans‐Georg 
Published: March 2007

AbstractAb‐restricted, H‐Y‐specific T cell clones from C57BL/6 mice were found to use predominantly Vβ6 T cell receptor genes, conferring Mls‐1a reactivity. However, the expression of Mls‐1a as a self antigen in (DBA/2 × C57BL/6)F1 mice did not turn these mice into nonresponders to H‐Y. Instead of Vβ6, they used other T cell receptor genes in this response. Thus, self tolerance appears to bias the repertoire of T cell receptor genes used in response to foreign antigens, without necessarily impairing the immune responsiveness to these antigens.
Cloned T cells provide help for malaria‐specific polyclonal antibody responses
Authors: Dean Goldring J. P. , Brake David A. , Cavacini Lisa A. , Long Carole A. , Weidanz William P. 
Published: March 2007

AbstractAthymic mice grafted with antigen‐reactive cloned T cells and challenged with Plasmodium chabaudi adami produced antibodies against multiple parasite antigens. Antibody reactivities were similar to those seen in infected euthymic mice and contrasted with their absence in infected athymic mice. These results suggest that it will not be possible to determine the antigenic specificity of clonal T cell populations in malarial infections by their capacity to provide help to restricted populations of B lymphocytes.
The abnormal T lymphocytes in lpr mice transcribe interferon‐γ and tumor necrosis factor‐α genes spontaneously in vivo
Authors: Murray Lesley , Martens Christine 
Published: March 2007

AbstractThe autoimmune mouse strain MRL/MPJ/lpr/lpr is characterized by accumulation of an abnormal T cell population which does not express CD4 or CD8 surface antigens. These cells were thought to be immunologically inert based on their inability to proliferate in response to a variety of T cell mitogens. We investigated the capacity of these cells to express lymphokine genes using a sensitive RNase protection assay. RNA was isolated from abnormal T cells which were purified directly from diseased animals, either as CD4−/CD8− or as fluorescence‐activated cell sorter‐isolated B220/Thy‐1 cells. These RNA preparations contained no detectable interleukin (IL)2, IL4, IL5 or IL6 transcripts, but did contain transcripts of genes for interferon‐γ and tumor necrosis factor‐α. Thus, this expanded population of abnormal cells spontaneously expresses these two lymphokines which have many interacting effects on the immune system, and may have important roles in the pathogenesis of autoimmune disease in lpr mice.
Isoelectric focusing of bovine major histocompatibility complex class II molecules
Authors: Watkins David I. , Shadduck John A. , Rudd Christopher E. , Stone Marc E. , Lewin Harris A. , Letvin Norman L. 
Published: March 2007

AbstractSerological approaches have been relatively unsuccessful in defining the allelic products of the bovine major histocompatibility (MHC) class II loci. We demonstrate that bovine class II allelic products can be characterized by precipitation with a polyclonal antiserum and separation using one‐dimensional isoelectric focusing. Polymorphic β chains were present in immunoprecipitates from both biosynthetically and surface‐labeled lectin‐stimulated bovine T cells. Precipitates from biosynthetically labeled but not surface‐labeled T cells contained a basic invariant chain and a non‐polymorphic structure. The non‐polymorphic structure appears to be a β chain. The polymorphic class II β chain co‐segregated with bovine MHC class I allelic products in a half‐sibling family, providing evidence for linkage between bovine class I and class II loci. This approach to the biochemical analysis of the bovine class II structures should facilitate the investigation of the association between the bovine products and disease susceptibility.
Organization and orientation of a human T cell receptor δ chain V gene segment that suggests an inversion mechanism is utilized in its rearrangement
Authors: Takihara Yoshihiro , Champagne Eric , Ciccone Ermanno , Moretta Lorenzo , Minden Mark , Mak Tak W. 
Published: March 2007

AbstractA human T cell receptor (TcR) δ chain variable region segment, Vδ3, has been mapped 2 kilobases 3′ to the constant (Cδ) gene. The Vδ3 gene segment is in an inverted transcriptional orientation to the diversity regions (Dδ), joining regions (Jδ) and Cδ gene segments. Analyses of TcR δ cDNA clone, KT041, showed that Vδ3 is linked to Dδ1, Dδ2, Jδ3 and Cδ and that this message encodes a potentially functional TcR δ chain. These findings indicate that a functional TcR δ gene can be constructed through a chromosomal inversion, suggesting that in human, chromosomal inversion is one of the important rearrangement mechanisms.
Human tonsillar dendritic cell‐induced T cell responses: analysis of molecular mechanisms using monoclonal antibodies
Authors: King Philip D. , Katz David R. 
Published: March 2007

AbstractDendritic cells, isolated from human tonsillar tissue, were found to be potent stimulators of the sodium periodate T cell oxidative mitogenesis reaction. Monoclonal antibodies against CD2, CD4, CD11a, CD18, LFA‐3, ICAM‐1, class I and class II major histocompatibility complex (MHC) inhibited T cell proliferation in this response, whereas antibodies against CD8, CD11b, CD11c and CD16 had no effect. Further, antibodies against CD2, CD11a, CD18, LFA‐3 and ICAM‐1 inhibited the early dendritic cell‐T cell clustering event which occurs in this cell interaction. In contrast, antibodies against CD4, class I and class II MHC did not inhibit clustering. Studies examining the expression of the respective molecules upon isolated dendritic cells and T cells suggest that anti‐LFA‐3 and anti‐class II MHC antibodies inhibit at the level of the dendritic cell, whereas anti‐CD2 and anti‐CD4 antibodies inhibit at the level of the T cell. However, antibodies against CD11a, CD18, ICAM‐1 and class I MHC may inhibit at either or both cell levels.These findings have enabled us to propose a molecular mechanism for dendritic cell‐T cell interaction in oxidative mitogenesis. Dendritic cell‐T cell clustering is mediated by bidirectional binding of LFA‐1 (CD11a and CD18) and ICAM‐1 (involving both molecules on both cell types) and unidirectional binding of CD2 and LFA‐3 (involving T cell CD2 and dendritic cell LFA‐3). This initial event permits a second interaction of dendritic cell and T cell molecules, involving T cell CD4, class I MHC (possibly at both cellular levels) and dendritic cell class II MHC, which deliver the signal for proliferation.
Definition of the thymic generative lineage by selective expression of high molecular weight isoforms of CD45 (T200)
Authors: Pilarski Linda M. , Gillitzer Reinhard , Zola Heddy , Shortman Ken , Scollay Roland 
Published: March 2007

AbstractSelective expression of CD45 isoforms distinguishes naive and memory T cells in peripheral blood. Paradoxically, although the most recent thymic emigrants are CD45R+ CD45 p180−, the majority of thymocytes are CD45 p180+. Speculating that the small subset of thymocytes selectively expressing only the high molecular weight isoforms of CD45 constitute the thymic generative lineage giving rise to peripheral T cells, we characterized the phenotypic and functional properties of CD45 p180− thymocytes. All cells bearing CD45 p180 were removed by rigorous depletion or all CD45R+ thymocytes were removed in a parallel depletion. CD45R− thymocytes were essentially the same in phenotype and CD4/CD8 subset distribution as unfractionated thymus, and dissimilar to naive peripheral blood lymphocyte (PBL) T cells. In contrast, CD45 p180− thymocytes, mainly CD45R+, were CD1− CD38− pgp 1+, corresponding closely to the phenotype of naive CD45R+ PBL T cells. This subset is enriched in CD4+ or CD8+ single positives, includes a high proportion of CD4−8− thymocytes which are predominantly CD3−, and appears to have a medullary location. Approximately 40%–50% of CD45 p180− thymocytes expressed a high density of CDw29 (4B4), which in the periphery is expressed at high density only on CD45 p180+ memory T cells and at low density on CD45R+ naive T cells. However, the expression of high density CDw29 in the absence of CD45 p180 indicates a close resemblance to fetal lymphocytes and suggests an essential role for CDw29 in both the least and the most mature of T cells. If CD45 p180− thymocytes constitute the generative lineage and CD45 p180+ cells are commited to intrathymic death, then the CD45 p180− subset should have enhanced proliferative potential. By combining depletion methods with a limiting dilution assay for clonogenic potential, we found that 100% of the clonogenic precursors present in unfractionated thymus were CD45R+ CD45 p180− cells. This indicates that the CD45 p180+ majority of thymocytes has a very limited capability for proliferation consistent with a commitment to intrathymic death. The clonogenic potential of CD45 p180− thymocytes indicates a greater functional resemblance to PBL T cells than to CD45 p180+ thymocytes. In so far as clonogenic potential in vitro reflects generative potential in vivo, expression of high molecular weight CD45 isoforms appears to define the generative thymic lineage. Our working hypothesis proposes that expression of CD45 p180 implements the mechanism for eliminating thymocytes with self‐reactive receptor specificities.
Cytotoxic T lymphocyte recognition of HLA‐A2 antigens in normal and HLA‐Cw3‐transgenic mice
Authors: Hämmerling Günter J. , Hunt Thurman , Dill Othmar , Moreno José 
Published: March 2007

AbstractIt is well established that a large fraction of murine cytotoxic T cells can recognize allogeneic major histocompatibility complex (MHC) antigens, and that the majority of this response are not restricted by H‐2 antigens of the responding host. In contrast, the murine response against the xenogeneic HLA class I antigens is relatively weak. Moreover, a large proportion of the responding murine T cells do not recognize the HLA antigen per se but only in an H‐2‐restricted manner, probably as an HLA peptide bound to H‐2.Considerable evidence suggests that in mice the T cell repertoire is selected by thymic H‐2 antigens. Therefore, we asked the question whether in transgenic mice expressing an HLA class I antigen the T cell repertoire would be shaped toward a more effective recognition of other HLA alleles. Normal C57BL/6 (B6) and HLA‐Cw3 ‐transgenic B6 mice were immunized with a B6‐derived cell line transfected with HLA‐A2. The resulting A2‐specific CTL were tested on L cells transfected with either A2 alone, which should identify the H‐2‐unrestricted CTL, and on L cells transfected with A2 plus H‐2b genes, which should identify the sum of H‐2b‐restricted and unrestricted CTL. Both bulk culture and limiting dilution experiments showed that the CTL precursor frequencies for A2‐specific CTL were not increased in the transgenic mice, and that both strains produced comparable proportions of H‐2b‐restricted and of unrestricted A2‐specific CTL. The B6.Cw3 mice seemed to respond less well to HLA‐A2 than the normal B6 mice, suggesting the possibility of tolerance for peptides shared by the Cw3 and A2 molecules. In conclusion, the T cells in the B6.Cw3 transgenic mice did not seem to be selected towards a stronger and more unrestricted recognition of an allo‐HLA antigen. The possible reasons are discussed.
Novel structures CTLA‐2α and CTLA‐2β expressed in mouse activated T cells and mast cells and homologous to cysteine proteinase proregions
Authors: Denizot François , Brunet Jean‐François , Roustan Paul , Harper Katherine , Suzan Marie , Luciani Marie‐Françoise , Mattei Marie‐Geneviéve , Golstein Pierre 
Published: March 2007

AbstractDifferential screening of a subtracted cDNA library led to the detection of two distinct but homologous mouse cDNA, called CTLA‐2α and CTLA‐2β. The corresponding transcripts have a tissue distribution restricted to T lymphocytes, where they are inducible upon activation, and to mast cells. The open‐frame regions of both cDNA encode proteins homologous to cysteine proteinase precursors, remarkably, however, only to the proregion of these. The ctla‐2α and ctla‐β genes both map to the C1 band of mouse chromosome 13. Sequence comparisons suggest that the proregion of an ancestor proteinase gene evolved to the ctla‐2 genes by successive duplications, first to autonomy, then to amplification. These results raise the question of the possible role of cysteine proteinase proregions, of cysteine proteinases themselves and of inhibitors thereof in activated T lymphocytes; from a different point of view, they also show that some protease proregions may have evolved as autonomous modules.
Expression and characterization of the interleukin 2 receptor in Theileria parva‐infected bovine lymphocytes
Authors: Coquerelle Therese M. , Eichhorn Margarete , Magnuson Nancy S. , Reeves Raymond , Williams Richard O. , Dobbelaere Dirk A. E. 
Published: March 2007

AbstractWe have previously shown that interleukin 2 receptors (IL 2R) are constitutively expressed on the surface of bovine lymphocytes infected with the parasite Theileria parva (Dobbelaere, D. A. E. et al., Proc. Natl. Acad. Sci. USA 1988. 85: 4730). In the present work we characterized these further and showed that IL 2R (Tac antigen) gene expression depended on the continuous presence of the parasite in the host cell cytoplasm. By Northern blot analysis we showed that elimination of the parasite, using a specific theilericidal drug, led to the arrest of Tac antigen mRNA expression. We also investigated receptor internalization and reappearance after receptor‐mediated endocytosis. Binding of human recombinant interleukin 2 (hrIL 2) to the bovine IL 2R caused rapid internalization of the surface IL 2/IL 2R complex. Approximately 50% of 125I‐labeled hrIL 2 was internalized within 10 min. The reappearance of surface IL 2R after ligand‐mediated endocytosis was also studied. Fifty percent of the maximum level of free IL 2R reappeared within 1–1.5 h, but approximately 12 h were needed to restore normal levels of free IL 2R expression after blocking with excess unlabeled hrIL 2.
T lymphocyte heterogeneity in old and young mice: functional defects in T cells selected for poor calcium signal generation
Authors: Philosophe Ben , Miller Richard A. 
Published: March 2007

AbstractAn increase in cytoplasmic free calcium ion concentration is thought to play a critical role in the entry of resting T lymphocytes into the mitotic cycle. Not all murine T cells, however, generate such a calcium signal when exposed to mitogenic doses of concanavalin A (Con A), and the proportion of nonresponsive cells increases with age in adult mice. Since the frequency of T cells able to generate cytotoxic or lymphokine‐secreting cells in culture also declines in old age, we have speculated that the defect in changes in Ca2+ concentration might underlie this functional deficit. To examine the relationship between functional competence and the calcium signaling pathway, we performed limiting dilution analyses of T cells enriched (by a fluorescence‐based cell‐sorting method) for high or low calcium signal generation. We found that rapid Ca2+ signal generation after Con A exposure did indeed correlate well with functional competence in Con A‐stimulated limiting dilution cultures. Furthermore, selection for Ca2+ signals induced by anti‐CD3 antibody, or even by ionomycin, similarly enriched for the functionally competent set of T cells. The ionomycin result, in particular, suggests that the difference between the reactive and nonreactive sets of T cells is unlikely to result simply from alterations in receptor‐linked signal transduction pathways. We discuss a model in which immune senescence involves an age‐dependent increase in a subset of T cells in which changes in cytoplasmic Ca2+ concentration are relatively difficult to induce by either receptor‐dependent mitogens or ionophores.
Recombinant human interleukin 5 is a selective eosinophil chemoattractant
Authors: Wang Ji Ming , Rambaldi Alessandro , Biondi Andrea , Chen Zhen Guo , Sanderson Colin J. , Mantovani Alberto 
Published: March 2007

AbstractHuman recombinant interleukin (IL) induced migration across polycarbonate filters of human peripheral blood eosinophils. The contribution of chemotaxis vs. chemokinesis was investigated using a checkerboard design with both polycarbonate and nitrocellulose filters. When different cytokine concentrations were seeded above and below the filter, maximal induction of migration required a positive concentration gradient between the lower and upper compartments of the chamber, though some gradient‐independent augmentation of migration occurred. These results indicate that induction of eosinophil migration across filter involves actual chemotaxis. The effect of IL 5 was selective for eosinophils with no effect on neutrophils and monocytes. Conversely, granulocyte‐macrophage colony‐stimulating factor elicited migration of both eosinophils and neutrophils. Thus, human IL 5 is a potent and selective chemoattractant for human eosinophils. Eosinophils are selectively localized in tissues under a variety of physiological and pathological conditions. Locally produced IL 5 may play a role in the selective recruitment of eosinophils from the blood compartment.
T cell responses to fractionated Mycobacterium leprae antigens in leprosy. The lepromatous nonresponder defect can be overcome in vitro by stimulation with fractionated M. leprae components
Authors: Ottenhoff Tom H. M. , Converse Paul J. , Gebre Negussie , Wondimu Assefa , Ehrenberg John P. , Kiessling Rolf 
Published: March 2007

AbstractProtective immunity against Mycobacterium leprae is dependent on M. leprae‐reactive T lymphocytes. M. leprae‐directed T cell reactivity is high in the localized tuberculoid form of leprosy but specifically absent in the disseminated lepromatous type of the disease.Two important questions that are relevant for the understanding of the immune response in leprosy as well as for the design of rational immunoprophylaxis and ‐therapy strategies are: (a) what are the antigens that trigger T cell responses in tuberculoid patients and thus protect these individuals from developing lepromatous leprosy and (b) is it possible to restore T cell responsiveness to M. leprae in lepromatous patients by rechallenging the immune system with selected antigens that will trigger help but not suppression? We have addressed these question by directly probing the peripheral T cell repertoire of 10 tuberculoid and 18 lepromatous patients with large numbers of different M. leprae and BCG antigenic components that had been separated on the basis of their relative molecular mass (Mr) by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and electroblotted onto nitrocellulose. This technique allows the identification of T cell‐stimulating antigens independent of the expression of B cell epitopes by these antigens. So far T cell epitopes have only been mapped on M. leprae proteins that had previously been defined by antibodies. Our results show that: (a) tuberculoid patients' T cells responded preferentially to M. leprae and BCG antigens in the lower (i.e. < 70 kDa) Mr range with a peak in the 10–25 kDa range; (b) 6 out of 18 lepromatous patients that did not respond to whole M. leprae responded strongly to isolated M. leprae components; antigens in the lower Mr. range were recognized by five out of these six patients and thus commonly seen by both tuberculoid and lepromatous patients' T cells; however, antigens in the higher Mr range, in particular > 150 kDa, were only recognized by lepromatous patients' T lymphocytes; (c) furthermore, the T and B cell repertoires in leprosy patients are skewed towards different antigenic fractions.
Induction of an activation antigen on human endothelial cells in vitro
Authors: Leeuwenberg Jet F. M. , Jeunhomme Trudi M. A. A. , Buurman Wim A. 
Published: March 2007

AbstractThis study describes the expression characteristics of a cell membrane protein recognized by a monoclonal antibody ENA1, which was obtained by immunizing mice with human umbilical vein endothelial (HUVE) cells cultured with a mixture of interleukin 1 and tumor necrosis factor‐α. The expression of this ENA1 antigen could also be induced by lipopolysaccharide and phorbol esters. Expression was only demonstrated on HUVE cells and human umblical arterial endothelial cells, pretreated with one or with a mixture of these reagents. No expression was detected on human fibroblasts, renal epithelial cells or on mesothelial cells derived from omental tissue, either pretreated or not with the aforementioned inducers of the antigen. Furthermore, no reactivity was observed with either polymorphonuclear cells, peripheral blood lymphocytes or the monocytic cell line U937. Time course experiments revealed that the expression of the ENA1 antigen was time dependent. Maximal expression on HUVE cells was observed after 5 h of incubation with activator, after which a decline in expression occurred.Induction of expression could be completely blocked by the mRNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide, indicating that de novo synthesis occurs. Other pharmacological reagents tested had no effect on the induction of ENA1 expression. The putative role of the newly described antigen is discussed in relation to the current knowledge of molecules involved in adhesion of immune cells in inflammatory processes.
Antibodies to HLA class I promoter‐binding proteins in sera from patients with systemic lupus erythematosus
Authors: Bouteiller Philippe Le , Auphan Nathalie , Weill Bernard , Lemonnier Franç Ois A. 
Published: March 2007

AbstractAntibodies directed against human cell nuclear factors (HLA‐F1 and HLA‐F2) that bind to the interferon consensus sequence (ICS) in the promoter region of the HLA‐A2 class I gene can be detected in the serum of some patients with systemic lupus erythematosus (SLE). Such antibodies, in gel‐shift assays, inhibited the formation of the retarded band corresponding to the HLA‐F1/F2‐ICS complex irrespective whether purified factors or crude nuclear extracts were used. This inhibitory effect was due to IgG since the SLE serum activity bound to and could be eluted from a protein A‐Sepharose column. This effect still persisted after absorption of SLE serum on a DNA‐affinity column which removed antibodies directed against protein‐free HLA‐A2‐ICS nucleotide sequence also present in such sera. Western blot analysis further confirmed that SLE serum recognized both HLA‐F1 (65 kDa) and HLA‐F2 (88 kDa) polypeptides, independently of the presence of the HLA‐A2‐ICS nucleotidic sequence, as well as other proteins. These results suggest that human sera from some patients with SLE may be used as a convenient source of antibodies directed against DNA‐binding proteins regulating gene transcription.