bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dna fragmentation and cell death mediated by t cell antigen receptor/cd3 complex on a leukemia t cell line*
Authors: Takahashi Shuji , Maecker Holden T. , Levy Ronald 
Published: March 2007

AbstractAn anti‐T cell receptor (TcR) monoclonal antibody (mAb), LC4, directed against a human leukemic T cell line, SUP‐T13, caused DNA fragmentation (“apoptosis”) and cell death upon binding to this cell line. Cross‐linking of receptor molecules was necessary for this effect since F(ab')2, but not Fab', fragments of LC4 could induce cell death. Five anti‐CD3 mAb tested also caused apoptosis, but only when they were presented on a solid phase. Interestingly, soluble anti‐CD3 mAb induced calcium flux and had an additive effect on the calcium flux and interleukin 2 receptor expression induced by LC4, but these anti‐CD3 mAb reversed the growth inhibition and apoptosis caused by LC4. The calcium ionophore A23187, but not the protein kinase C activator phorbol 12‐myristate 13‐acetate (PMA), also induced apoptosis, suggesting that protein kinase C activation alone does not cause apoptosis, although PMA is growth inhibitory. These results suggest that two distinct biological phenomena can accompany stimulation of the TcR/CD3 complex. In both cases, calcium flux and interleukin 2 receptor expression is induced, but only in one case is apoptosis and cell death seen. The signal initiating apoptosis can be selectively prevented by binding CD3 portion of the receptor in this cell line. This difference in signals mediated by the TcR/CD3 complex may be important in explaining the process of thymic selection, as well as in choosing anti‐TcR mAb for therapeutic use.
Different large deletions of t cell receptor vβ genes in natural populations of mice*
Authors: Jouvin‐Marche Evelyne , Trede Nikolaus S. , Bandeira António , Tomas Alfredo , Loh Dennis Y. , Cazenave Pierre‐André 
Published: March 2007

AbstractA panel of geographically separate Mus m. domesticus and Swiss mice from several sources was screened for deletions in the T cell receptor variable (V) β locus. Four out of forty‐three strains tested show a deletion identical to or larger than the deletion previously described in SJL mice. To our knowledge, this is the first time that such important Vβ deletions are described in inbred or partially inbred wild‐derived strains of mice. On the other hand there seems to be very little polymorphism between the remaining Vβ genes. Expression of Vβ genes in peripheral and intra‐thymic T cells was tested using antibodies specific for different Vβ polypeptide chains. Flow cytometry analysis revealed a high expression of Vβ6 and Vβ17 genes in the Copacabana Swiss‐derived strain and an absence of Vβ17 expression in the WLA wild‐derived strain.The three Mus m. domesticus strains (WLA, DDO and WBG) having deleted two to three additional Vβ subfamilies compared to SJL present no apparent immune deficiencies or autoimmune disorders. We conclude that relatively few Vβ genes may suffice for unimpaired survival of wild mice and that there is a selective pressure for the structural conservation of the remaining Vβ genes.
T cell receptor expression on immature thymocytes with in vivo and in vitro precursor potential
Authors: Nikolic‐Zugic Janko , Moore Mark W. 
Published: March 2007

AbstractImmature CD8‐CD4‐ double‐negative (DN) thymocytes differentiate intrathymically into CD8+CD4+ and CD8‐CD4+ thymocytes and migrate to the periphery. This differentiation proceeds through several intermediate phenotypic changes in the expression of CD8 and CD4. We have recently established the existence of a CD8loCD4lo cell population in murine thymus that can repopulate the irradiated thymus in vivo and differentiate rapidly in vitro to CD8+CD4+ double‐positive (DP) cells. The CD8loCD4lo cells score as DN upon direct cytofluorometric analysis, yet are distinct from true DN cells by various criteria. Experimental evidence strongly suggests that they are descendants of true DN in the maturation pathway. In the experiments presented here, we further characterize this CD8loCD4lo thymocyte population. Northern blot and RNA protection analysis reveal that these cells transcribe full length mRNA for the T cell receptor (TcR)α chain, unlike the less mature interleukin 2 receptor‐positive DN thymocytes. Surface expression of the TcR‐associated CD3 molecule occurs on ∼ 15% of these cells at low levels characteristic of immature cells. In the course of in vitro differentiation a vast majority (∼ 80%) of these cells convert to CD8+CD4+ and significant numbers of the brightly staining DP convertants (11%–34% on day 1 and 48%–68% on day 2) express immature levels of CD3. Our results indicate that CD8lo, CD4lo cells might be the first thymic subset to rearrange TcR α chain genes and express TcR α/β heterodimer on the surface at levels characteristic of immature cells. Furthermore, the surface expression of TcR persists on the in vitro progeny of these thymocytes.
T cell activation: independent induction of killing activity and interleukin 2 secretion in cytolytic hybridomas*
Authors: Ozery Tali , Berke Gideon , Moscovich Miriam , Ozato Keiko , Kaufmann Yael 
Published: March 2007

AbstractMemory‐like cytotoxic T lymphocytes (CTL) hybridomas exhibiting inducible killing activity and IL2 production were used to analyze the anamnestic response of CTL. Four activating agents were examined; anti‐Thy‐1 monoclonal antibody G7, staphylococcal enterotoxin B, interferon (IFN)‐α/β and IFN‐γ. These agents seemed to affect CTL activities in three distinct ways. Anti‐Thy‐1 monoclonal antibody, like specific antigen, was found to be a potent inducer of specific killing and IL2 production, whereas staphylococcal enterotoxin B induced IL2 production, but not cytolytic activity. On the other hand, IFN‐α/β and IFN‐γ effectively stimulated cytotoxicity without inducing IL2 production. The independent triggering of specific killing and IL2 secretion in the monoclonal cytolytic hybridomas suggests that in CTL distinct signals stimulate killing activity and IL2 production. The results also suggest that IFN‐α/β and IFN‐γ trigger the cytolytic program through an alternative activation pathway which does not involve the T cell receptor.
The lymphocyte‐specific protein tyrosine kinase p56lck is hyperphosphorylated on serine and tyrosine residues within minutes after activation via T cell receptor or CD2
Authors: Danielian Silvia , Fagard Remi , Alcover AndrÉS , Acuto Oreste , Fischer Siegmund 
Published: March 2007

AbstractHuman T cells can be activated and induced to proliferate through either the antigen‐specific receptor complex (TcR‐CD3) or the CD2 surface molecule. Following stimulation, both serine and tyrosine phosphorylation of cellular protein have been demonstrated to occur. p56lck, a protein tyrosine kinase associated to the inner face of the plasma membrane, is almost exclusively expressed in lymphoid cells, especially T cells. Within minutes after activation of a human T cell‐derived line (Jurkat) via stimulation of either the TcR‐CD3 complex or the CD2 glycoprotein, we observed a hyperphorphosylation of p56lck. A concomitant shift to a higher molecular weight in sodium dodecyl sulfatepolyacrylamide gel was also observed. Similar changes were obtained with phorbol 12‐myristate 13‐acetate. Tryptic phosphopeptide analysis of the hyperphosphorylated form of p56lck yielded new phosphorylated sites in serine residues and an increased tyrosine phosphorylation. These results suggest that p56lck may be intimately connected to the signaling pathway in T cell activation.
In vivo administration of interleukin 1 elicits increased Ia antigen expression on B cells through the induction of interleukin 4
Authors: Killar Loran M. , Hatfield Cheryl A. , Carding Simon R. , Pan Mary , Winterrowd Gregory E. , Bottomly Kim 
Published: March 2007

AbstractThe effects of the in vivo administration of interleukin 1 (IL 1) on lymphocytes from lymph node and spleen were analyzed. Mice received five daily subcutaneous (s.c.) injections of various doses of human recombinant IL 1β. Either 1 or 7 days after IL 1 treatment, spleens, popliteal and inguinal lymph nodes were collected. Lymphadenosis and splenomegaly were observed in the IL 1‐treated animals. Lymph nodes from IL 1‐treated mice contained a higher percentage of B cells than controls, and B cells from IL 1‐treated mice expressed dramatically increased levels of Ia antigen. Lymphadenosis and splenomegaly, as well as the changes in subset distributions and Ia expression were transient. Concomitant treatment of mice with IL 1 and anti‐IL 4 monoclonal antibody suppressed IL 1 effects on B cell Ia expression, but not on the B/T cell ratio. In situ hybridization analyses revealed that IL 1 treatment induced the expression of mRNA for IL 4, interferon‐γ, and IL 2 in lymph node and spleen cells. The distribution of cells expressing the various cytokine mRNA was markedly different between the spleens and lymph nodes.
Expression and function of CD2 during murine thymocyt
Authors: Yagita Hideo , Asakawa Jun‐Ichi , Tansyo Shigeru , Nakamura Tetsuya , Habu Sonoko , Okumura Ko 
Published: March 2007

AbstractCD2, originally recognized as the sheep erythrocyte receptor of human T cells, has been implicated in early T cell development in the thymus. In this report, we examined the expression and functional role of CD2 during murine thymocyte ontogeny by using monoclonal antibodies to murine CD2. Surface expression of CD2 was first detected in Thy−1+ fetal thymocytes at day 14 of gestation and it progressively increased during CD4−CD8− phenotype. Surface IL 2 receptor (CD25) expression was readily detected in surface CD2− cells at day 13 of gestation and the majority of CD2+ cells appeared to be generated from CD25+ cells thereafter. In adult CD4−CD8− thymocytes, the expression of CD2 and CD25 was mutually exclusive. These results indicate that surface CD2 expression is not a prerequisite for CD25 induction during murine thymocyte ontogeny. This was further confirmed by fetal thymus organ culture in which anti‐murine CD2 mAb was included. The antibody treatment led to a suppressed CD2 expression on thymocytes; however, there was no effect on the appearance of CD25. Moreover, no influence on the development of mature CD3+ thymocytes was observed after fetal thymus organ culture in the presence of anti‐murine CD2 mAb, and a substantial number of CD3+CD2− cells was demonstrated in fetal and adult CD4−CD8− thymocytes. These findings argue against the functional relevance of CD2 expression during early T cell development as proposed in humans.
Immunological alterations inducible by mercury compounds. III. H‐2A acts as an immune response and H‐2E as an immune “suppression” locus for HgCl2‐induced antinucleolar autoantibodies
Authors: Mirtcheva Jasmina , Pfeiffer Christiane , Bruijn Jan Anthonie De , Jacquesmart FrÉDÉRic , Gleichmann Ernst 
Published: March 2007

AbstractIn responder mouse strains repeated injections of subtoxic doses of HgCl2 induce formation of antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANolA). Others have shown that responsiveness to HgCl2‐induced formation of ANA and ANolA is linked to H‐2. Here, we extend these studies to a variety of mouse strains not tested previously. After confirming that strain B10.S (H‐2s) is a high responder we have shown that strains B10.D2 (H‐2d) and B10.BR (H‐2k) are nonresponders. By comparing a panel of strains carrying appropriate intra‐H‐2 recombinant haplotypes derived from d, k and s, we were able to map responsiveness to As. Interestingly, among four strains all of which were As, and thus responsive, only the two H‐2E‐ ones, B10.S and B10.RSD2, were high responders whereas the two H‐2E+ ones, B10.HTT and B10.S(9R), were significantly less responsive. Thus, the genetics of HgCl2‐induced autoantibody formation follow the rules established for immune responses to a variety of different antigens in that expression of H‐2E “suppressed” the response.
Recombinant interleukin (IL) 2‐induced human B cell differentiation is mediated by autocrine IL6
Authors: Xia Xing , Lee Hern‐Ku , Clark Steven C. , Choi Yong Sung 
Published: March 2007

AbstractThe molecular mechanism of the interleukin (IL) 2‐induced differentiation of human B cells has been investigated. The experimental results show that Staphylococcus aureus Cowan strain I (SAC) activation alone induces IL 6 secretion from B cells. When B cells were activated by SAC, there was an increased transcription of the IL 6 mRNA. It reached the peak level by 6 h and rapidly decreased to an undetectable level within 24 h. The IL 6 concentration in the culture supernatants reached the peak at 24–48 h and decreased slightly in the following culture periods. Since IL 2 alone could induce IgG secretion, whether exogenous IL 6 was added or not, and IL 2 did not increase autocrine IL 6 synthesis, it appears that IL 2 induces the IL 6 responsiveness of SAC‐activated B cells to differentiate in the later stage of the culture. The addition of polyclonal anti‐IL 6 antibody inhibited IgG secretion. The antibody still efficiently blocked IgG secretion up to day 5, indicating an important role of autocrine IL 6 in the IL 2‐driven B cell differentiation. However, the saturation dose of anti‐IL 6 antibody inhibited 50%–70% of IgG secretion, suggesting that IL 2‐induced B cell differentiation appears to be mediated by other factors besides IL 6.
Serum immunoglobulin levels and naturally occurring antibodies against carbohydrate antigens in germ‐free BALB/c mice fed chemically defined ultrafiltered diet
Authors: Bos Nicolaas A. , Kimura Hirohisa , Meeuwsen Cornelia G. , Visser Hendrik De , Hazenberg Maarten P. , Wostmann Bernard S. , Pleasants Julian R. , Benner Robbert , Marcus Donald M. 
Published: March 2007

AbstractThis study investigates the influence of exogenous antigenic stimulation on the serum immunoglobulin levels and the levels of circulating natural antibodies against carbohydrate antigens. Thus, BALB/c mice, raised in a germ‐free environment and fed a chemically defined, ultrafiltered diet (GF‐CD), were employed. These mice had normal serum IgM levels, but IgG and IgA levels were approximately 5% of conventionally reared littermates. The concentrations of all four IgG isotypes were equally low. The variable part of the heavy chains of naturally occurring BALB/c antibodies against a number of carbohydrate antigens, including 3‐fucosyllactosamine (3‐FL), levan and dextran, are encoded by VH441, and these antibodies express cross‐reactive idiotopes recognized by the monoclonal antibodies 6C4 and 6B1. Antibodies against levan and dextran were lower in GF‐CD than in conventional mice, but levels of anti‐3FL antibodies, and 6C4 and 6B1 idiotopes, were comparable to those in conventional animals. Peptidoglycan polysaccharide complexes (PPC) are carbohydrate antigens of bacterial origin, like levan and galactan. Naturally occurring antibodies against PPC were found in the serum of conventional mice, but were severely reduced in GF‐CD mice. The results indicate that most naturally occurring antibodies against carbohydrate antigens of bacterial origin found in conventional mice are caused by exogenous stimulation.
Identification by sequence analysis of chemotactic factors for monocytes produced by normal and transformed cells stimulated with virus, double‐stranded RNA or cytokine
Authors: Damme Jo Van , Decock Benny , Lenaerts Jean‐Pierre , Conings René , Bertini Riccardo , Mantovani Alberto , Billiau Alfons 
Published: March 2007

AbstractA monocyte chemotactic activity was found to be released by various types of cultured human cells after appropriate stimulation: normal diploid fibroblasts, peripheral blood mononuclear cells or monocytes isolated therefrom, and a number of tumor cell lines, including osteosarcoma (MG‐63) and hepatoma (Malavu) but not melanoma (Bowes) cells. Cultures of diploid human fibroblasts and these tumor cells stimulated with interleukin (IL) 1 or double‐stranded RNA [poly(rI)·poly(rC)], or infected with viruses (measles or rubella viruses) were found to produce chemotactic activity for both monocytes and granulocytes. Media collected from fibroblasts treated with E. coli or IL 6 did not contain such activity.Granulocyte and monocyte chemotactic activities were serologically distinct, and could be separated by successive chromatographical procedures. While the granulocyte chemotactic activity of both fibroblasts and MG‐63 cells had previously been identified as granulocyte chemotactic protein/IL 8, the monocyte chemotactic activity from MG‐63 cells was identified by amino acid sequence analysis as a different protein recently described to be released by human glioma and myelomonocytic cell lines. In view of the similarity in their chromatographical behavior, monocyte chemotactic activities from fibroblasts, MG‐63 cells and fresh monocytes can probably be assigned to identical molecules. Cultures of unfractionated peripheral blood cells, however, were found to release an additional monocyte chemotactic protein, identifiable by amino acid sequence analysis as platelet factor 4.
Human interleukin 2 (IL 2) receptor β chain allows transduction of IL 2‐induced proliferation signal(s) in a murine cell line
Authors: Doi Takeshi , Hatakeyama Masanori , Minamoto Seijiro , Kono Takeshi , Mori Hisashi , Taniguchi Tadatsugu 
Published: March 2007

AbstractInterleukin 2 (IL 2) delivers cell growth signal by virtue of its interaction with the high‐affinity receptor complex, which consists of two distinct IL 2‐binding molecules: the IL 2 receptor α (IL 2R α) and β (IL 2R β) chains. Unlike many known growth factor receptors, neither of the IL 2R chains seems to contain a tyrosine kinase domain. In this report, we have shown that the human IL 2R β chain expressed in a murine IL 3‐dependent, non‐lymphoid cell line can transduce IL 2‐induced cell proliferation signal(s) in combination with the autologous mouse IL 2R α chain. This observation should provide a tool to dissect IL 2‐induced signal transduction pathway in lymphoid and non‐lymphoid cells.
Localization of interleukin 6 mRNA in human tonsils by in situ hybridization
Authors: Bosseloir Alain , Hooghe‐Peters Elisabeth L. , Heinen Ernst , Cormann Nadine , Kinet‐Denoël CÉCile , Vanhaelst Luc , Simar LÉOn 
Published: March 2007

AbstractWe have investigated which areas produce interleukin 6 (IL 6) in human tonsils. This growth factor is required for the terminal differentiation of B lymphocytes into plasmocytes. Using 35S‐labeled IL 6 cDNA we demonstrated IL 6 gene expression over various areas of the tonsils, with consistent exception of the follicles, by in situ hybridization. It is, therefore, proposed that B cells are stimulated during their migration out of the follicles.
Accessory factors involved in murine T cell activation. Distinct roles of interleukin 6, interleukin 1 and tumor necrosis factor
Authors: Vink Anne , Uyttenhove Catherine , Wauters Pierre , van Snick Jacques 
Published: March 2007

AbstractInterleukin (IL) 6 was compared to other macrophage‐derived products for its capacity to support the proliferation of accessory cell‐depleted T cells. Monoclonal anti‐IL 6 antibodies were found to inhibit completely the “accessory activity” of macrophage supernatants, thus demonstrating the central role played by IL 6 in T cell activation. IL 6 was apparently more critical for initiating than in maintaining T cell proliferation because anti‐IL 6 antibodies lost all inhibitory activity when added late to the culture. Moreover, IL 6 was not the only accessory factor required for optimal T cell proliferation. Using low‐density cultures to minimize the number of contaminating accessory cells, we found that significant proliferation of CD4 cells was obtained only in the presence of both IL 6 and IL 1. In contrast, with CD8 cells substantial proliferation was obtained with IL 6 alone. This response could, however, be enhanced by IL 1. Tumor necrosis factor (TNF) and granulocyte/macrophage colony‐stimulating factor showed no activity in these assays. The concentrations of IL 1 and of IL 6 required to support optimal proliferation were 10 pg/ml and 1 ng/ml, respectively.Analysis of the mechanisms underlying T cell activation by IL 1 and IL 6 indicated that both cytokines were required for optimal production of IL 2 but that IL 6 alone was sufficient to confer IL 2 responsiveness. For CD8 cells, this effect was observed with doses of IL 6 about 100 times lower than those required for the induction of IL 2 secretion (0.001 vs. 0.1 ng/ml). TNF, which was not capable of inducing IL 2 secretion, was also found to induce IL2 responsiveness but only at a concentration ≈ 1000 times higher than that of IL 6. In accordance with these observations, IL 6 and to a lesser extent TNF were found to enhance IL 2R expression by CD8 cells. Interestingly, this enhancing effect was totally dependent on the presence of IL 2.
In vitro transformation by Epstein‐Barr virus induces a switch in growth factor and anti‐IgM responsiveness in a human leukemic B cell clone
Authors: Janssen Ottmar , Gillis Steven , Kabelitz Dieter 
Published: March 2007

AbstractBy in vitro transformation with Epstein‐Barr virus (EBV), we have previously established EBV lymphoblastoid cell lines (LCL) from a patient with leukemic centrocytic B cell lymphoma. EBV‐transformed LCL and EBV genome‐negative leukemic B cells showed identical chromosome aberrations and IgH gene rearrangements. In the present study we have analyzed the effect of exogenous cytokines [interleukin (IL) 1, 2, 3, 4, 6, tumor necrosis factor, lymphotoxin, transforming growth factor β, (TGF‐β)] and anti‐IgM antibodies on the in vitro proliferation of EBV− leukemic B cells and EBV‐converted LCL. In contrast to conventional chronic lymphocytic leukemia, B cells of the patient DUL spontaneously proliferated for up to two weeks in the absence of exogenous lymphokines. The spontaneous proliferative capacity of clonal DUL B cells was not modulated by IL 1, IL 3, IL 6, TNF or LT. In vitro growth of DUL B cells was increased, however, by exogenous recombinant (r)IL 2, and was abrogated by TGF‐β, rIL 4 and anti‐IgM. rIL 4 not only inhibited spontaneous B cell proliferation but also neutralized the enhancing effect of rIL 2. In contrast, growth of the EBV‐transformed DUL LCL was not affected by any of these factors. These data demonstrate that in vitro infection and transformation of a clonal B cell population by EBV induces a switch in responsiveness to rIL 4, TGF‐β and anti‐IgM. In addition, this report is the first to demonstrate an inhibitory effect of rIL 4 on a spontaneously proliferating human leukemic B cell clone.
Selective expression of Vδ6 genes by B2A2− CD4− CD− T cell receptor γ/δ thymocytes
Authors: Miescher Guido C. , Liao Nan Shih , Lees Rosemary K. , MacDonald H. Robson , Raulet David H. 
Published: March 2007

AbstractMost CD4−CD8− adult murine thymocytes characterized by absence of the B2A2 (J11d) antigen express T cell receptors (TcR) α/β and utilize preferentially Vβ8.2 segments. To a much lesser extent, B2A2−CD4−CD8− thymocytes also express TcR γ/δ, as evidenced by biochemical and Northern blot analysis. We have now been able to exclude the possibility that these cells might co‐express both types of TcR: Vβ8 B2A2− CD4−CD8− thymocytes expressed no TcR δ mRNA whereas the corresponding Vβ8− subset transcribed full‐length TcR γ as well as δ mRNA. Furthermore, the TcR γ/δ expressing B2A2− thymocytes were found to use preferentially Vδ6 genes. Conversely, they did not express Vδ5 genes which are most frequently used by other TcR γ/δ‐bearing populations such as B2A2 CD4− CD8− thymocytes or CD4−CD8− peripheral lymph node cells. RNase protection experiments showed that two particular Vδ6 transcripts predominate in these γ/δ populations, the most prominent Vδ6 sequence being highly homologous if not identical to Vα7.1. Our observations extend previous information on overlapping Vα and Vδ gene repertoires, particularly in the cross‐hybridizing Vα7/Vδ6 gene family. Moreover, our data suggest that B2A2−CD4−CD8− thymocytes represent a developmentally unique subset in which both Vδ and Vβ segments are nonrandomly expressed.