bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Radioresistant” intrathymic T cell precursors express T cell receptor Cγ4‐ and Cδ‐specific gene messages
Authors: Kishihara Kenji , Yoshikai Yasunobu , Matsuzaki Goro , Tomooka Suguru , Nomoto Kikuo 
Published: March 2007

AbstractWe have studied the expression and sequences of T cell receptor γ and δ chain gene messages in intrathymic T cell precursors of mice irradiated with 600 rads. On day 7 after irradiation a high level of expression of γ and δ chain messages was detected in thymocytes which were composed of a relatively high proportion of CD3+CD4−CD8‐thymocytes. During further development of the precursors from day 7 to day 14 after irradiation, γ and δ chain messages fell to low levels and α and β mRNA levels increased. Nucleotide sequence analysis of 14 γ and 10 δ chain complementary DNA (cDNA) in the thymocytes on day 7 revealed that there were 7 functional γ chain transcripts composed of Vγ2‐Jγ2‐Cγ2 or Vγ1‐Jγ4‐gene segments, and only 1 functional δ chain transcript composed of the VδM23‐Dδ1‐Dδ2‐Jδl‐Cδ gene segments. The repertoire of γ chain and δ chain genes used in “radioresistant” intrathymic T cell precursors of adult mice appears to be limited.
Induction of T cell serine proteinase 1 (TSP‐1)‐specific mRNA in mouse T lymphocytes
Authors: Simon Hans‐Georg , Fruth Uli , Eckerskorn Christoph , Lottspeich Friedrich , Kramer Michael D. , Nerz Gabi , Simon Markus M. 
Published: March 2007

AbstractAn oligonucleotide probe corresponding to nucleotides of a cDNA encoding the T cell‐associated proteinase 1 (TSP‐1) was chosen to study the induction and expression of TSP‐1‐specific transcripts in mouse T lymphocytes and tissues. We demonstrate that TSP‐1 mRNA is only expressed in activated T lymphocytes and is absent from all mouse tissues tested including those containing resting mature T lymphocytes. Expression of the TSP‐1 gene was observed in T lymphoctes in vitro in response to either phorbolester (phorbol 12‐myristate 13‐acetate), Ca2+ ionophore (A23187), lectin or alloantigen. In general, TSP‐1 mRNA appeared and peaked later compared to interleukin 2 transcripts. Furthermore, TSP‐1 mRNA was inducible in vitro in both Ly‐2+ and L3T4+ lymphocyte populations treated with alloantigen and/or lectin. The transcription of the TSP‐1 gene was always accompanied by the expression of proteinase activity. High expression of TSP‐1 transcripts was also observed in in vivo derived T effector cells specific for lymphocytic choriomeningitis virus. However, TSP‐1 mRNA was predominantly associated with virus‐specific Ly‐2+ T cells and correlated with their proteinase and cytolytic activities. The data suggest that TSP‐1 gene transcription is a useful marker to characterize T effector cells in vitro and in vivo.
Stromal cell lines which support lymphocyte growth: characterization, sensitivity to radiation and responsiveness to growth factors
Authors: Pietrangeli Carolynn E. , Hayashi Shin‐Ichi , Kincade Paul W. 
Published: March 2007

AbstractStromal cells which grow as an adherent layer of Whitlock‐Witte cultures are thought to be an essential component of the lymphohemopoietic microenvironment. Stromal cell lines from bone marrow (BM) and spleen have been obtained by treatment of cultures with 5fluorouracil and selected for their lymphocyte support capacity by measuring the clonal growth of stromal cell‐dependent lymphocyte lines in methyl cellulose.Established stromal cell lines differed significantly from stromal cells in primary Whitlock‐Witte cultures with respect to expression of certain hemopoietic cell surface markers. For example, the Thy‐1 and Mac3 antigens were expressed by stromal cell lines obtained from BM and spleen, but not by stromal cells in primary cultures. Features common to all stromal cells include synthesis of actins, the neural adhesion molecule N‐CAM, and a variety of collagens. Two types of common leukocyte antigens were not significantly expressed.The proliferation and total protein synthetic capacity of lymphocyte‐supportive stromal cell lines was sensitive to ionizing radiation. After exposure of the cells to 200 rads, the incorporation of either [3H]thymidine or [3H]Leucine was reduced to less than 50% of control values, but the growth of lymphocytes was augmented in the presence of an irradiated stromal cell layer.The proliferation of stromal cell lines was also affected by exposure to a variety of growth factors. Addition of epidermal growth factor or endothelial cell growth factor augmented BM or spleen‐derived stromal cell proliferation, while interferon‐γ had the opposite effect. In general, but not exclusively, lymphocyte growth was inhibited by factors which augmented the proliferation of stromal cells.Novel methods are described for isolating stromal cells and determining their capacity to support lymphocyte growth in vitro. Evidence is presented that this ability is not restricted to BM‐derived stromal cells. The function of stromal cells was not dependent on their ability to proliferate, and this may be modulated by immunoregulatory and other growth factors.
Complex regulation of the T cell receptor α gene: three different modes of triggering induction
Authors: Wilkinson Miles F. , Macleod Carol L. 
Published: March 2007

AbstractThe T cell receptor (TcR) for antigen is composed of variable α and β subunits in noncovalent association with the invariant T3 multimer. TcR/T3 transcripts accumulate in a specific sequence during T cell development; TcR α transcripts are the last in the series to accumulate. To explore the regulation of TcR α gene expression, we investigated a T lymphoma cell clone which constitutively expresses TcR β, T3 † and T3 e mRNA, but essentially lacks detectable TcR α mRNA. The cell clone can be induced to accumulate substantial amounts of TcR α mRNA in response to phorbol myristate acetate (PMA) or calcium ionophore A23187. Two different protein synthesis inhibitors also induce TcR α mRNA. The following evidence indicates that PMA, A23187 and cycloheximide induce TcR α by different mechanisms: (a) treatment with a combination of two agents induces greater than additive amounts of TcR a mRNA than that induced by a single agent; (b) the immunosuppresent cyclosporin A specifically inhibits A23187‐mediated TcR α mRNA induction, whereas it fails to inhibit PMA or cycloheximide‐mediated induction; and (c) both A23187 and PMA increase the rate of TcR α gene transcription, while cycloheximide influences TcR α mRNA accumulation by post‐transcriptional mechanisms.
Functional differentiation and repertoire diversification of T cells derived from single progenitor cells
Authors: Kina Tatsuo , Amagai Takashi , Nishikawa Shin‐Ichi , Araya Shin‐Ichi , Katsura Yoshimoto 
Published: March 2007

AbstractFunctions of T cells derived from single progenitor cells were investigated. B10. Thy‐1.1 recipient mice were either whole body‐irradiated and marrow reconstituted or thymus‐shielded, irradiated and marrow reconstituted, and limited numbers (3 × 103 or 6 × 103) of a 1:1 mixture of bone marrow cells from C57BL/6 and B6.Lyt‐2.1 mice were transferred intrathymically (i.t.). Donor‐type (Thy‐1.2+) cells of the thymus of a small portion of recipients which expressed the phenotype of either Ly‐2.2 or Ly‐2.1 but not both were regarded to be a clone of T cells derived from a single progenitor cell, and such clones were assayed for polyclonal helper (Th) and polyclonal cytolytic (CTL) activities as well as alloantigen‐specific proliferative (mixed lymphocyte reaction; MLR) and CTL activities. Clones taken 4 weeks after transfer (4‐week‐old clones) which were generated in the thymus of whole body‐irradiated recipients showed polyclonal CTL but not polyclonal Th activity, whereas 4‐week‐old clones generated in the thymus of thymus‐shielded recipients showed both polyclonal CTL and Th activities. Similarly, 4‐week‐old clones generated in whole body‐irradiated recipients responded with CTL to alloantigens when induced in the presence of T cell growth factors but not with MLR, whereas 4‐week‐old clones generated in thymus‐shielded recipients showed both MLR and CTL to alloantigens. Repertoire difersifi‐cation of 4‐week‐old clones, however, was incomplete, since clones generated in whole body‐irradiated recipient did not necessarily respond with CTL to all alloantigens examined, and those generated in thymus‐shielded recipients did not necessarily respond with MLR to all the antigens. On the other hand, T cell clones were shown to fully mature by 7 weeks after transfer in terms of cell function as well as repertoire diversification.
The Y chromosome from autoimmune BXSB/MpJ mice induces a lupus‐like syndrome in (NZW × C57BL/6)F1 male mice, but not in C57BL/6 male mice
Authors: Izui Shozo , Higaki Megumu , Morrow Dwight , Merino Ramon 
Published: March 2007

AbstractThe Y chromosome of the BXSB mouse has been shown to be responsible for the acceleration of lupus‐like autoimmune syndrome in inbred BXSB mice and in their F1 hybrids with NZB or NZW mice. To further define the role of this as yet unidentified gene linked to the BXSB Y chromosome, designated Yaa (Y chromosome‐linked autoimmune acceleration), the Y chromosome was transferred from the BXSB strain to nonautoimmune C57BL/6 (B6) mice. The effect of the Yaa gene on the autoanti‐body formation and the development of glomerulonephritis was investigated in B6 mice and in their F1 hybrids with NZW mice. The presence of the BXSB Y chromosome was not able to induce significant autoimmune responses in B6 mice. However, (NZW × B6)F1 males bearing the BXSB Y chromosome developed a severe lupus‐like autoimmune syndrome, as documented by the production of anti‐DNA antibodies and gp70‐anti‐gp70 immune complexes and the development of lethal lupus nephritis. Both sexes of (NZW × B6)F1 hybrids without the BXSB Y chromosome were essentially normal. Our results suggest that (a) the BXSB Y chromosome by itself is not sufficient to initiate autoimmune responses in nonautoimmune B6 mice, and (b) it is able to induce autoimmune responses in mice potentially capable of developing the disease, but whose autosomal abnormality by itself is not sufficient to develop autoimmune diseases.
Specific lysis by CD8+ T cells of Schwann cells expressing Mycobacterium leprae antigens
Authors: Steinhoff Ulrich , Kaufmann Stefan H. E. 
Published: March 2007

AbstractIn vitro cultured murine Schwann cells which were devoid of class I and class II gene products of the major histocompatibility complex expressed class I, though not class 11, antigens after stimulation with recombinant interferon‐γ. Recombinant 1FN‐γ‐stimulated Schwann cells after priming with M. leprue were lysed by antigen‐specific CD8+ T lymphocytes in vitro. These findings suggest that specific lysis of M. leprae‐infected Schwann cells by CD8+CTL plays a role in leprosy.
Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus
Authors: Saint‐Remy Jean‐Marie R. , Lebecque Serge J. , Lebrun Philippe M. , Jacquemin Marc G. 
Published: March 2007

AbstractFrom the serum of 10 allergic subjects we have prepared IgG antibodies recognizing idiotopes carried by specific antibodies to Dermatophagoides pteronyssinus (Dpt) allergens, and studied cross‐reactivity of anti‐Dpt IgG bystander and antigen‐binding site‐associated idiotopes by latex agglutination assays. Idiotopes of specific anti‐Dpt IgE were evaluated by radioimmunoassays. Depending on the assay, a binding or inhibition of more than 50%, as compared to the reactivity of specific antibodies with the corresponding anti‐idiotypic (anti‐Id) IgG, was considered significant. Cross‐reactivity of antigen‐binding site‐associated idiotopes attained a mean proportion of 6/10 for IgG and 9.6/10 for IgE. By contrast, bystander idiotopes cross‐reacted only occasionally with a mean proportion of 2/10 for both IgG and IgE antibodies. Anti‐Id antibodies from two subjects have been isolated by adsorption on insolubilized anti‐Dpt antibodies of the corresponding patient. Using this purified material we have confirmed that (a) the majority of anti‐Id antibodies carry an “internal image” of the initial antigen and compete in a dose‐dependent manner with Dpt allergens for the binding to the anti‐Dpt antibodies and (b) paratope‐associated idiotopes of anti‐Dpt antibodies are shared by unrelated individuals.
Structure and rearrangement of the T cell receptor J alpha locus in T cells and leukemic T cell lines
Authors: Champagne Eric , Sagman Uri , Biondi Andrea , Lewis William H. , Mak Tak W. , Minden Mark D. 
Published: March 2007

AbstractThe vast majority of T cells express an antigen receptor (TcR) composed of an α/β heterodimer. The α and β chains are encoded for by a set of variable (V), joining (J) and constant (C) region genes. Unlike the J genes of the β chain which are limited in number and are clustered close to the constant region, the Jα, genes are spread over an 85‐kilobase DNA region, upstream of the C, gene. We have isolated the complete J, locus, bounded on the 5' side by the C sequence of the 6 gene and on the 3' side by the C sequence of the a gene. The experiments described here demonstrate that the J gene segments extend 75 kb 5' of Cα, and participate equally in generating the diversity of the a chain in peripheral T cells. Similarly, in leukemic T cell lines, rearrangements occurred over the entire locus and involved both alleles. Densitometry data suggest that in most peripheral T cells both alleles also are rearranged; thus, allelic exclusion in the α locus does not occur at the level of rearrangement. In three cell lines, an rearrangement has occurred on one allele in a region located 10 kb from the 5' end of the locus.
Functional T cell receptor δ chain gene messages in athymic nude mice
Authors: Yoshikai Yasunobu , Matsuzaki Goro , Takeda Yasuyuki , Ohga Shouichi , Kishihara Kenji , Yuuki Hiroyuki , Nomoto Kikuo 
Published: March 2007

AbstractThe rearrangement and expression of T cell antigen receptor (TcR) δ chain genes were investigated in congenitally athymic nude mice. The lymphoid cells derived from nude mice showed evidence of rearranged δ chain genes and a relatively high level of δ chain gene messages. Nucleotide sequence analysis revealed that nude mice contained an in‐frame δ chain transcript, composed of Vδ5‐Dδ1‐Dδ2‐Jδ1‐Cδ genes in the spleen. We have previously described functionally rearranged TcR γchain genes in the spleen of nude mice. Taken together, T cell precursors appear to proliferate and differentiate along the extrathymic pathway into TcR γ/δ‐bearing T cells in nude mice.
Profiles of lymphokine activities and helper function for IgE in human T cell clones
Authors: Maggi Enrico , Prete Gianfranco Del , Macchia Donatella , Parronchi Paola , Tiri Antonio , Chrétien Isabelle , Ricci Mario , Romagnani Sergio 
Published: March 2007

AbstractA large panel of phytohemagglutinin (PHA)‐induced T cell clones (690 in total), established from four different human lymphoid tissues (peripheral blood, tonsils, lymph nodes and spleens) by a high‐efficiency cloning technique, was characterized according to their pattern of lymphokine production. The majority of both CD4+ and CD8+clones from all lymphoid tissues produced interleukin (IL) 2 and/or interferon (1FN)‐γ response to 24‐h stimulation with PHA. In contrast, higher proportions of IL4‐producing clones were found among CD4+clones from tonsils and spleens than from peripheral blood and lymph nodes, whereas only a minority of CD8+ clones from all lymphoid tissues were found to produce IL4.It was not possible to divide the CD4+ (helper/inducer) clones on the basis of their pattern of lymphokine activity into two clear‐cut groups analogous to Thl and Th2 helper clones described in mice. Although 21 out of 503 (4%) CD4+ T cell clones produced IL4, but not IFN‐γ or IL2, and 208 (41%) produced IL2 and/or IFN‐γ, but not IL4, a total number of 185 (37%) CD4+ clones showed the ability to produce IL4 plus IL2 and/or IFN‐γ.All types of CD4+ T cells (as classified according to their pattern of lymphokine activity) provided help for IgG production in allogeneic B cells. In contrast, helper function for IgE was detectable only among the IL4‐producing clones. However, the proportion of CD4+ clones providing help for IgE synthesis was significantly lower among those producing IL4 and IFN‐γ or IL4, IL2 and IFN‐γ than among those producing IL4 alone or IL4 and IL2.Thus, a clear‐cut dichotomy between IL4‐ and IFN‐γ‐producing Th cells, as found in mice, does not seem to exist in humans. However, IL4 and IFN‐γ, even if not always produced by distinct T cell subsets, appear to regulate reciprocally the synthesis of IgE in humans as well.
Definition of the RFLP alleles in the human immunoglobulin IGHG gene locus
Authors: Ghanem Nada , Lefranc Marie‐Paule , Lefranc Gerard 
Published: March 2007

AbstractIn order to define more precisely the polymorphism of the human immunoglobulin IGHG (Cγ) genes and, consequently, to understand the structure and evolution of this multigene family, we have investigated the Restriction Fragment Length Polymorphisms (RFLP) of the IGHG genes in 113 unrelated individuals and 18 families. Using the restriction enzymes Bam HI, Sac I and Eco RI, and hybridization to a IGHG probe and to a specific IGHG3 (Cγ3) probe, we describe 47 different restriction fragments (RF) in the IGHG locus, allowing us to define at least 15 RFLP alleles for the different IGHG genes. Our data demonstrate that the restriction fragment length polymorphism is occasionally due to the presence or absence of a given restriction site as a consequence of a point mutation, such as the creation of an Eco RI site, at the codon 3 of exon 2 in one IGHG4 allele (IGHG4*D2). However, most of the RFLP we observed seem to result from the insertion or deletion of a few hundred base pairs as illustrated by the IGHG3 polymorphism.
Interleukin 4 instructs uncommitted B lymphocytes to switch to IgGl and IgE
Authors: Bergstedt‐Lindqvist Susanne , Moon Hee‐Bom , Persson Ulla , Möller Göran , Heusser Christoph , Severinson Eva 
Published: March 2007

AbstractMouse interleukin 4 (IL4) is a T cell‐produced lymphokine with multiple effects on different cells types of the hematopoietic lineages. IL4 has pronounced effects on B lymphocytes, where it induces high levels of IgGl and IgE secretion in lipopolysaccharide‐stimulated cultures that would otherwise secrete predominantly IgG3 and IgG2b (of the non‐IgM isotypes). An important question is how IL4 exerts its effect. Two main possibilities exist: (a) IL4 instructs uncommitted B lymphocytes to IgGl and IgE production; (b) IL4 selects and expands an already precommitted B cell. In this study we show, by the use of limiting dilution analysis, that IL4 dramatically increases the precursor frequency of IgGl and IgE‐secreting cells with no significant effect on the clone size, clearly suggesting that IL4 instructs uncommitted B cells to switch to IgGl and IgE. The fraction of total Ig precursors that can switch to the two isotypes is furthermore high. The high precursor frequency for IgE obtained in the presence of IL4 further demonstrates that IL4 is an important modulator of IgE responses.
Autoantibody production is associated with polyclonal B cell activation in autoimmune mice which express the lpr or gld genes
Authors: Ishigatsubo Yoshiaki , Steinberg Alfred D. , Klinman Dennis M. 
Published: March 2007

AbstractSystemic autoimmune disease in humans and mice is characterized by hypergamma‐globulinemia and abnormally high levels of serum autoantibodies. The presence of certain genes, such as the lpr and gld genes, induces otherwise normal mice to spontaneously develop systemic autoimmunity. To better understand the effect of these genes on the development hypergammaglobulinemia, we quantitated the absolute number of splenic B cells producing antibodies reactive with each of four autoantigens and two conventional antigens and compared this to the total number of Ig‐secreting spleen cells present in these mice. Whereas autoimmune mice had significantly greater numbers of autoantibody‐secreting spleen cells than normal mice, they also had significantly greater numbers producing antibodies of conventional specificity. When expressed as a proportion of the total repertoire, no bias towards autoantibody production was present when autoimmune lpr and gld animals were compared to their congenic nonautoimmune C57BL/6 and C3H/HeJ counterpartsWe also examined the B cell repertoires of recombinant inbred mice derived by mating autoimmune NZB with normal NFS mice. Some recombinant inbred (RI) lines developed hypergammaglobulinemia and produced large quantities of autoantibody. While evidence for specific (auto) antigenic stimulation was present in some RI lines, hypergammaglobulinemia was commonly associated with polyclonal B cell activation in these autoimmune mice as well.
A requirement for the CD5 antigen in T cell activation
Authors: Mcateer Michael J. , Lagarde Anne‐Catherine , Georgiou Harry M. , Bellgrau Donald 
Published: March 2007

AbstractTreatment of adult rats with a monoclonal antibody specific for the CD5 antigen led to a dramatic reduction in the number of CD5+ cells. However, a substantial number of T cells remained as assessed by other T cell‐specific antibodies. These CD5− T cells did not proliferate in response to alloantigen or mitogenic stimulation, did not generate cytotoxic T lymphocytes in vitro, and did not induce graft‐vs.‐host disease when injected into susceptible recipients in vivo. Re‐expression of the CD5 antigen occurred when CD5‐ T cells were placed in an environment devoid of the anti‐CD5 antibody. Re‐expression of the antigen was followed by return of the T cell proliferative responses.While CD5− T cells could not proliferate in response to alloantigen they could produce interleukin 2 following a short pulse with the T cell mitogen concanavalin A. However, T cell proliferative or cytotoxic responses could not be rescued by the addition of an exogenous source of interleukin 2. We conclude that the CD5 antigen appears to be required for proliferation of resting T cells.
Division of human helper T cells into two sets on the basis of the induction of anti‐tumor cytotoxicity by phorbol ester and calcium ionophore
Authors: Pawelec Graham , Bush Friedrich , Reinhold Uwe , Rehbein Arnika , Balko Irene , Bühring Hans‐Jörg 
Published: March 2007

AbstractFourteen noncytotoxic human helper T cell clones were examined for autocrine proliferative responses and cytotoxicity to tumor cells after stimulation with 12‐0‐tet‐radecanoylphorbol 13‐acetate (TPA) and ionomycin (Io). Although all clones responded to alloantigen, they could be divided into two groups based on their proliferative response or lack of it to TPA/Io. Nonresponders could not be converted to responder status by addition of interleukin (IL) 1 or indomethacin to the cultures. Responder status did not correlate with any of the following properties of the clones: originating donor, recognitive specificity, B cell helper activity, proliferative response to IL2 or 4, lymphokine secretory capacity or density of expression of antigen receptors, CD4 or HLA class II molecules. Responder status did, however, correlate with the ability of TPA/Io to induce major histocompatibility complex‐unrestricted cytolytic activity directed towards natural killer‐resistant tumor cells. These results divide human helper cells into two types on the basis of induction of anti‐tumor cytotoxicity.