bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive splenic B cell activation in IgMtransgenic mice
Authors: Forni Luciana 
Published: March 2007

AbstractTwo lines of IgMtransgenic mice were analyzed for the state of activation of their splenic compartment, with regard to the frequency of large cells in the different lymphoid subpopulations, and to the isotype distribution of background plasma cells. We observed an extensive B cell activation preferentially involving B lymphocytes co‐expressing transgenic and endogenous IgM (IgD), and resulting in massive immunoglobulin classswitch. Nearly all splenic plasma cells contain endogenous immunoglobulins, withfrequencies of IgG and IgA plasma cells significantly higher than in normal mice. There are virtually no plasma cells that produce only the transgenic IgM. Moreover, only a proportion ofplasma cells producing endogenous immunoglobulins co‐express the transgenic product. In addition to these observations that apply to both transgenic lines, differences were found between the two lines concerning the quantitative expression of the transgenic IgM, the frequency of cells expressing the transgene and the magnitude of switch. These data are indicative of the complexity of the IgMtransgenic mouse model, in which the phenomenology may depend on the transgene insertional position, on B cell physiology and on immunological mechanisms of recognition, induction and regulation.
A CD4+ TH2 cell line isolated from mice chronically infected with Trypanosoma cruzi induces IgG2 polyclonal response in vivo
Authors: Spinella Sylviane , Milon Geneviève , Hontebeyrie‐joskowicz Mireille 
Published: March 2007

AbstractIn our study we describe further characteristics of a CD4+ T cell line (G‐05) isolated from lymph nodes of C3H/HeJ mice chronically infected with Trypanosoma cruzi. This T cell line secreted lymphokines such as interleukin (IL)4 and IL 5 and could be defined as a TH2 type of helper T cells. By passive transferinto naive mice, the G‐05 line was able to induce a polyclonal B cell activation in the spleen. This splenic B cell activation was quite similar to that seen in chronically T. cruzi‐infected animals, where the isotypic pattern presents a large increase of IgG2a and IgG2b isotypes. Moreover, it was possible to reproduce this kind of polyclonal B cell activation in vivo, with the supernatant of G‐05 T cells cultured in the presence of T. cruzi extract, accessory cells andexogenous IL2. Analysis of this supernatant showed the presence of large amounts of IL 4,IL 5, IL 3 and IL 6 but not of interferon‐γ, and residual IL 2 activity was not significant. These results suggest that the G‐05 T cells considered as TH2 cells on the basis of their lymphokine production are involved in the development of the in vivo polyclonal B cell activation in T. cruzi infection.
Signaling through CD19, Fc receptors or transforming growth factor‐β: each inhibits the activation of resting human B cells differently
Authors: Barrett Thomas B. , Shu Geraldine L. , Draves Kevin E. , Pezzutto Antonio , Clark Edward A. 
Published: March 2007

AbstractTo understand further the roles that negative regulatory signals may play in B cell immune responses, we compared three inhibitors of B cell proliferation: cross‐linking CD19 with monoclonal antibody (mAb), signaling through Fc receptors by intact anti‐μ mAb, and transforming growth factor‐β (TGF‐β). Each agent was tested for its ability to block proliferation and specific activation events induced in human tonsilar B cells activated by either cross‐linking surface immunoglobulin, signaling through CD20, or direct activation of protein kinase C (PKC) by phorbol 12‐myristate 13‐acetate. We found that each inhibitor was functionally distinct. Bothanti‐CD19 mAb and anti‐μ mAb inhibited antiimmunoglobulin activated cells and anti‐CD20‐activated cells, but neither inhibited cells activated by phorbol 12‐myristate 13‐acetate. TGF‐β, on the other hand, inhibited equally profoundly cells activated by each of the three regimens. These results suggest that TGF‐β blocks B cell activation at a step following the activation ofPKC, whereas both signaling through CD19 and Fc receptor block early steps in the PKC activation pathway. Signaling through anti‐CD19 mAb was unique in that proliferation of anti‐immunoglobulin‐activated cells was reduced on day 3 and then augmented subsequently. With all other inhibitory combinations the block was permanent. We conclude that each of these three inhibitors has unique important functions and therefore suggest that the effectiveness of negative signaling in B cell immune regulation will dependon the combinations of specific inhibitors modulating a specific activation program.
Subsets of CD3+ (T cell receptor α/β or γ/δ) and CD3− lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood
Authors: Jarry Anne , Cerf‐bensussan Nadine , Brousse Nicole , Selz Françoise , Guy‐grand Delphine 
Published: March 2007

AbstractIntestinal intraepithelial lymphocytes (IEL) were studied, after isolation in humans for their surface antigens with a large variety of monoclonal antibodies. They show peculiar characteristics when compared with peripheral blood lymphocytes and intestinal laminapropria lymphocytes. Although a majority of human intraepithelial lymphocytes (IEL) express an α/β type of T cell receptor (TcR), 13% express a γ/δTcR, a percentage which was significantly higher than that found in blood and in lamina propria. In contrast to observations in mice, there was no evidence that normal human TcR γ/δ+ intestinal IEL might use preferential variable segments of γ genes. About 10% of human intestinal IEL expressed the α chain but not the β chain of CD8, thus resembling a subset of CD8 α+β− IEL, which was recently described in mice and found to be of thymoinde‐pendent origin. In addition, 10% of human IEL had a unique phenotype of immature T cells, as they bore only CD7, but no other T cell or natural killer cell markers. Finally, even the major population of IEL which expressed the usual markers of the T cell lineage (CD3,TcR α/β, CD2, CD4 or CD8 α/β) differed from peripheral blood T lymphocytes by their peculiar expression of surface antigens associated with activation. Indeed, 80% of IEL were CD45R0+, CD45A−, but co‐expression of CD11a, CD29 and LFA‐3 was inconstant. In addition, 90% of IEL expressed HML‐1.
Interleukin 2 production by a marmoset B cell Iine
Authors: Brent Lawrence H. , Miyawaki Toshio , Everson Michael P. , Butler Joseph L. 
Published: March 2007

AbstractSeveral B cell lines constitutively secreting interleukin (IL) 2 were derived from the Epstein‐Barr virus‐positive marmoset B cell line, B95–8. A representative line, KRC‐18, was cloned by limiting dilution and found to be 40% surface IgM+, 60% cytoplasmic IgM+, > 95% DR+, weakly Tac+ and devoid of T cell, monocyte and NK cell surface antigens. Supernatant from KRC‐18 cells supported the long‐term growth of an IL 2‐dependent murine T cell linc, HT‐2, and contained 7—8 units/ml of IL 2 activity when compared to recombinant IL 2. The supernatant was fractionated by Sephadex G‐75 gel filtration, and maximal proliferation of HT‐2 cells was supported by the 20—22‐kDa column fraction. The proliferative response of HT‐2 cellsto KRC‐18 supernatant was inhibited by monoclonal antibodies to human IL 2 or the murine IL 2 receptor in a dose‐dependent manner, suggesting that the KRC‐18IL 2 has epitopes that are similar to human IL 2, and that its activity is mediated through binding to the IL 2 receptor of the target cell line. When KRC‐18 cells were analyzed for cytoplasmic IL 2, >90% of the cells contained intracellular IL 2 in amountsequivalent to, or greater than, mitogen‐activated T cells. These data indicate that certain B lineage cell lines are capable of IL 2 synthesis and secretion.
Elevated expression of Pgp‐1 (Ly‐24) by murine peritoneal B lymphocytes
Authors: Murphy Timothy P. , Kolber Donna L. , Rothstein Thomas L. 
Published: March 2007

AbstractB cell expression of the surface glycoprotein, Pgp‐1 (Ly‐24), was evaluated using flow cytometric analysis. Pgp‐1 expression on naive, conventional (splenic) B cells was low but could be increased by mitogenic stimulation. Pgp‐1 expression on naive peritoneal B cells was higher than expression by unmanipulated conventionalB cells, suggesting the possibility that peritoneal B cells have been activated in vivo. However, the elevated expression of Pgp‐1 by peritoneal B cells was not accompanied by increased expression of surface Ia but was correlated with Ly‐1 status. Further, Pgp‐1 expression by B cells from germ‐free mice did not differ from that of normal animals. The elevated expression of Pgp‐1 by peritoneal B cellsis superficially similar to that provoked by mitogenic stimulation of conventional B cells; however, several characteristics suggest that the elevated expression of Pgp‐1 by peritoneal B cells does not reflect prior activation of these cells.
Cell components required for deletion of an autoreactive T cell repertoire
Authors: Fukushi Noriko , Wang Bingyan , Arase Hisashi , Ogasawara Kazumasa , Good Robert A. , Onoé Kazunori 
Published: March 2007

AbstractT cells become tolerant to self antigens during their development in the thymus. Clonal deletion of thymocytes bearing T cell receptor (TcR) which recognize self antigens is a major mechanism for generating tolerance. In the present study we have used allogeneic bone marrow (BM) chimeras, prepared with various combinations of mouse strains and focusing especially on expressions of I‐E molecules and Mls‐1a antigens on the cell surface, to investigate both immuno‐histochemically and by flow cytometry the cell components that contribute to the clonal deletion of T cells positive for Vβ6 TcR. The Vβ6 TcR expression is strongly associated with T cell recognition of both I‐E and Mls‐1a antigens. We found that I‐E+ cells derived from donor BM (and thus not of recipient lineage) represented a primary requirement for deletion of Mls‐1a−reactive thymocytes which bear Vβ6 TcR. Immunohistochemical analysis revealed that the donor‐derived I‐E+ cells were distributed mainly to the thymic medulla and that the Vβ6+ cells were eliminated from the thymic medulla between 2 and 3 weeks following BM transplantation. In contrast, Mls‐1a+ cells of either donor or recipient origin might be responsible for the deletion, even though cortical epithelial cells appeared not to express Mls‐1a antigens.
Primary responses of human T cells to mycobacteria: a frequent set of γ/δ T cells are stimulated by protease‐resistant ligands
Authors: Pfeffer Klaus , Schoel Bernd , Gulle Heinz , Kaufmann Stefan H. E. , Wagner Hermann 
Published: March 2007

AbstractT lymphocyte subsets expressing either T cell receptor α/β or γ/δ were selected from human peripheral blood T cells and proliferative responsesto molecular mass‐fractionated mycobacterial lysates were determined. α/β T cells primarily responded to fractions > 30 kDa whereas γ/δ Tcells preferentially reacted to fractions < 3 kDa. Protease digestion abolished the stimulating activities for α/β T cells, confirming that α/β Tcells respond to protein components. In contrast, components recognized by γ/δ T cells proved resistant to protease digestion. In limiting dilution studies, frequencies of proliferating γ/β T cells remained virtually unaltered by protease treatment of stimulating lysates, while those of α/β T cells became almost undetectable. Furthermore, only few γ/δ T cells responded to the 65‐kDa heat‐shock protein. Our data indicate that, unlike α/β T cells, γ/δ T cells respond to mycobacterial components which are resistant to vigorous protease digestion.
The activation of protein kinase C is not necessary for the monoclonalantibody‐induced modulation of CD3 and CD4 antigens
Authors: Thuillier Laure , Selz Françoise , Métézeau Philippe , Pérignon Jean‐louis 
Published: March 2007

AbstractWe studied the effect of staurosporine, a potent inhibitor of protein kinase C (PKC) activity, on the phorbol ester‐ or monoclonal antibody (mAb)‐induced modulation of CD3 and CD4 surface antigens. Staurosporine (10−5 M) completely inhibited phorbol ester‐induced modulation but had no effect on that induced by mAb. These results indicate that the down‐regulation of CD3 and CD4 observed after activation of the cells by the corresponding mAb is independent from PKC‐mediated phosphorylations, and thus that the activation of PKC is sufficient but not necessary to induce the modulation of CD3 and CD4 antigens.
Immune responses to defined epitopes of the circumsporozoite protein of the murine malaria parasite, Plasmodium yoelii
Authors: Grillot Didier , Michel Martine , Müller Ingrid , Tougne Chantal , Rènia Laurent , Mazier Dominique , Corradin Giampietro , Lambert Paul‐henri , Louis Jacques A. , del Giudice Giuseppe 
Published: March 2007

AbstractWe have investigated the immunogenicity of defined sequences of the circumsporozoite (CS) protein of the murine malaria parasite, Plasmodium yoelii. A 21‐mer synthetic peptide from the nonrepetitive region of the CS protein (position 59—79, referred to as Py1) induced T cell proliferative responses in H2d and, to a lesser extent, in H2b mice. Conversely, a synthetic peptide (referred to as Py4) consisting of four (QGPGAP) repeats of the P. yoelii CS protein, induced anantibody response only in H2b mice. No antibody response was observed whenthe Py3 peptide, consisting of three (QGPGAP) repeats, was used as an immunogen. When cross‐linked to the Py4 repetitive peptide, the Py1 sequence behaved as a T helper epitope allowing the production of anti‐Py4 antibodies in H2d mice. Several long‐term T cell lines and clones specific for the nonrepetitive Py1 peptide were originated in vitro from both H‐2d and H2b mice. These lines and clones were CD4+ and proliferated in a major histocompatibility complex‐restricted fashion. Furthermore, Py1‐specific T cell lines and clones did not proliferate in the presence of synthetic peptides from an analogous region of another rodent malaria parasite, P. berghei, despite the high degree of homology existing in this sequence of the two CS proteins. Finally, supernatants from 7 out of 13 clones (from BALB/c mice) produced detectable amounts of interleukin 2 and interferon‐γ; whereas supernatants from the 4 clones from C57BL/6 and 2 from BALB/c mice contained detectable amounts of interleukin 5. These results show that functionally heterogenous CD4+ T cell populations, belonging to either TH1 or TH2 subset, are activated upon immunization of mice with the P. yoelii Py1 synthetic peptide. It is not yet known what differential role these CD4+ subsets play during the malaria infection or after immunization with different malaria T cell epitopes. This knowledge may have a particular impact in the design of effective subunit vaccines against malaria.
Cell and type specificity of interferon action. Unusual characteristics of the transcriptional control of gene expression by interferon‐γ in T cells*
Authors: Gribaudo Giorgio , Gariglio Marisa , Cavallo Giorgio , Landolfo Santo 
Published: March 2007

AbstractWe have examined the mechanisms by which interferon (IFN)‐γ and IFN‐α regulate the expression of 2′‐5′‐oligoadenylate synthetase (2–5A synthetase) and class I major histocompatibility complex antigens in murine T cells and in cell types of other histological origin. When treated with IFN‐α both fibroblasts and T cell lines displayed a marked increase of the 2–5A synthetase activity and of the corresponding mRNA. The augmentation of the enzyme activityin T cells was induced by IFN‐α at the transcriptional level, as determined by nuclear run‐on analysis. In contrast IFN‐γ was capable of increasing 2–5A synthetase activity only in fibroblasts, but not in T cells. Nuclear run‐on assays revealed that the 2–5A synthetase gene in T cells is not transcriptionally activated by IFN‐γ. After IFN‐α and ‐γ treatment we also observed a significant increase in class I gene expression in fibroblasts and T cell lines as measured both on the cell surface and by cytoplasmic RNA accumulation. In the case of the T cell line, DO1110, the observed increase in the steady‐state levels of class I transcripts was a consequence of a high rate of H‐2 gene transcription as demonstrated by run‐on analysis. However, the molecular mechanisms involved in this IFN‐dependent H‐2 gene transcriptional activation are differentbetween IFN‐α and IFN‐γ. When the T cell lines DO1110, L12‐R4 and EL4 were transfected with a plasmid containing a reporter gene (chloramphenicol acetyltransferase) under the control of a regulatory IFN‐responsive DNA element of 237 bp or 1.4 kb, IFN‐α was able to activate the transcription of these constructs. In contrast, IFN‐γ did not recognize the IFN‐responsive element which, by itself, activated transcription of the reporter gene in response to IFN‐γ in other cellular types of non‐T cell origin. Therefore, in the T cell linesexamined, IFN‐γ increases the H‐2 gene expression by acting on DNA elements located upstream of the regulatory segment used in this study or downstream of thecap site. This suggests a possible cell specificity in the activation of an IFN‐responsive element, that in turn may regulate the IFN‐inducible gene expression in acell‐specific fashion. Thus, the differential biological activities of IFN‐γ on T cells could be generated by a differential gene activation at the transcriptional level.
Adoptive transfer of fluorescence‐labeled cells shows that resident peritonealmacrophages are able to migrate into specialized lymphoid organs and inflammatory sites in the mouse
Authors: Rosen Hugh , Gordon Siamon 
Published: March 2007

AbstractWe have examined the migration of murine macrophages from the vascular compartment tonormal and inflammatory tissues by the adoptive transfer of resident peritoneal macrophages (RPMΦ) fluorescently labeled with the hydrophobic dye 1,1′‐dioctadecyl3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI). After initial labeling of the plasma membrane of RPMΦ, the dye accumulated stably in intracellular vesicles of low density (Q = 1.042—1.045 kg/l) and cells remained viable in culture for 4 weeks. Like the normal monocyte, DiI‐RPMΦ, but not exudate‐derived or fixed cells, migrated to peritoneal exudates, following i.v. adoptive transfer, by a mechanism inhibitable by an antibody to the type 3 complement receptor. In the absence of an inflammatory stimulus there was no migration to the peritoneal cavity, and DiI‐RPMΦ, accumulated within 4 h in the red pulp and marginal zone of the spleen. By day 6 these cells still formed a tight ring of fluorescence in the marginal zonealone, outside the marginal metallophil cells. DiI‐RPMΦ injected into the peritoneal cavity migrated to the parathymic lymph nodes where they were found in the subcapsular sinus and in the medullary cords, whereas very few fluorescent cells could be found in the T cell areas. The migration of RPMΦ to lymphoid organs required viable cells but, unlike the recruitment of cells to peritoneal exudates, was not inhibitable by antibodies to CR3. We conclude that the RPMΦ is a useful surrogate for the analysis of constitutive and induced monocyte migration to secondary lymphoid and inflammatory sites, respectively.
Human suppressor T cell clones lack CD28
Authors: Li Shu Guang , Ottenhoff Tom H. M. , van den Elsen Peter , Koning Frits , Zhang Li , Mak Tak , De Vries René R. P. 
Published: March 2007

AbstractPreviously we showed that certain T cell lines and clones from a lepromatous leprosy patient displayed a dose‐dependent suppression of the proliferation of autologous T cells to Mycobacterium leprae (M. leprae) but not mitogen or an unrelatedantigen. The latter cells were also cloned and did not display this suppressive activity, were CD4+ and proliferated vigorously to M. leprae presented by autologous HLA‐DR molecules. We shall refer to these cells as T helper (Th) cells. Most of the suppressive T cell clones (Ts) were also CD4+ and also proliferated to M. leprae presented by HLA‐DR, but much less strongly than Th cells.In this study we report on our search for (a) the mechanism of this apparently antigen‐specific suppression by T cells, and (b) a possible phenotypic difference between Th and Ts clones. The two main conclusions are that Ts clones possess a lytic machinery, but that M. leprae‐specific suppression and cytotoxicity can be clearly dissociated, and that the only phenotypic difference between Th and Ts is the presence of the CD28 marker on Th and its absence on Ts clones.
Structure of class II genes in wild mouse Mus saxicola: functional and evolutionary implications
Authors: Cam Philippe , Jouvin‐marche Evelyne , Leguern Christian , Marche Patrice N. 
Published: March 2007

AbstractClass II β genes have been characterized from Mus saxicola, a wild mouse which diverged five millions years ago from the house mouse. The nucleotide sequences of the exons 2 and 3 of Eβ1, Aβ2 and Eβ2 genes have been determined in order to define the molecular mechanisms of interspecies variability. The Eβ1 and Aβ1 (J. X. She, personal communication) genes from Mus saxicola display extensive sequence variability in exon 2 when compared tothose of the house mouse, in association with the variability of residues probably involved in antigen binding. On the other hand, most putative T cell contact residues from the I‐Eβ chain, and to a lesser extent from the I‐Aβ chain, were found conserved in mice. T cell contact residues from Mus saxicola I‐Aβ and I‐Eβ chains are identical to those of the b and q, and of the k haplotypes of the house mouse, respectively. Comparisons performed withAβ2 and Eβ2 genes revealed that both are highly conserved and, in contrast to Aβ1 and Eβ1 genes, that a strong selective pressure for conservation occurs in the Aβ2 second exon. The different aspects of Aβ2 and Eβ2 genes evolution may correlate with the original function of their products. Comparisons of the intervening sequences revealed that the repeated motifs of the hotspot region present in the Eβ1b gene are also conserved in Mus saxicola. Recombinations may have occurred, in some cases in association with χ‐like sequences.
Human antigen‐specific memory T cells express the homing receptor (LAM‐1) necessary for lymphocyte recirculation
Authors: Tedder Thomas F. , Matsuyama Takami , Rothstein David , Schlossman Stuart F. , Morimoto Chikao 
Published: March 2007

AbstractLymphocytes must circulate from blood into lymphoid tissues and sites of infection and inflammation to function efficiently in vivo. This process of “homing” is in part directed by the expression of the leukocyte adhesion molecule (LAM‐1, also known as TQ1 and Leu‐8) in humans and the homologous MEL‐14 antigen in mice. In this report, we demonstrate that the LAM‐1 molecule is a 74‐kDaprotein and that only half of the CD4+ T cells in humans which have a memory phenotype (CD45RA −CD29hi) express the LAM‐1 molecule. Functionally, these two phenotypically distinct subpopulations of memory cells were quite different. The LAM‐1+ memory cells proliferated better to recall antigen and induced three to seven times higher levels of B cell immunoglobulin secretion than their LAM‐1− counterparts. Thus, antigen‐specific memory T cellswithin the helper lineage express the homing receptor appropriate for regulating their migration to secondary lymphoid tissues and sites of inflammation.