bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD8+ and CD45RA+ human peripheral blood lymphocytes are potent sources of macrophage inflammatory protein 1α, interleukin‐8 and RANTES
Authors: Conlon Kevin , Lloyd Andrew , Chattopadhyay Utpala , Lukacs Nicholas , Kunkel Stephen , Schall Thomas , Taub Dennis , Morimoto Chikao , Osborne Jennifer , Oppenheim Joost , Young Howard , Kelvin David , Ortaldo John 
Published: March 2007

AbstractThe chemokines macrophage inflammatory protein 1α (MIP 1α), interleukin‐8 (IL‐8) and RANTES are potent regulators of leukocyte trafficking. Examination of chemokine secretion by human peripheral blood lymphocytes after stimulation with anti‐CD3 or phorbol 12, 13 myristate acetate and ionomycin showed CD8+ cells were the dominant source of MIP 1α and RANTES. Although production of MIP 1α and IL‐8 were similar in pharmacologically stimulated CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ CD45RA+ cells, the largest amounts of MIP 1α and RANTES were secreted by CD8+ CD45RO+ lymphocytes. A parallel pattern of prolonged chemokine mRNA expression for at least 18 h after activation was observed in the T cell subsets. These results confirm that human T lymphocytes have a unique capacity for secretion of these three chemokines. In addition, CD8+ cells have an unrecognized role in recruiting cells to sites of inflammation, and adult human CD45RA+ cells have a physiologically significant secretory capacity.
Limited development capacity of the earliest embryonic murine thymus
Authors: Amagai Takashi , Itoi Manami , Kondo Yuichi 
Published: March 2007

AbstractPrevious studies have demonstrated that murine thymus separates from the pharynx during 11.5–12 days of gestation, and that the proliferation of thymic cells starts at this age. We characterized embryonic day 12 thymus in terms of the surface phenotype of the thymus cells, the function of the lobe in supporting T cell development in organ culture, and the precursor activity of the thymus cells in a mixed culture with deoxyguanosine‐treated lobes.The phenotype of the major population of embryonic day 12 thymus cells was HSA+, CD44+, c‐kit+, Thy‐1−, CD25−, CD4−, CD8−, TcR−, and Sca‐1−. In organ culture of embryonic day 12 thymus lobes, most of the lobes did not develop well and failed to generate CD4+CD8+, CD4+CD8−, or CD4−CD8+ cells, even when embryonic day 14 thymus cells were added. However, thymus cells on embryonic day 12 contained T cell precursors that developed into mature T cells in co‐culture with deoxyguanosine‐treated fetal thymic lobes. The majority of the stromal cells in deoxyguanosine‐treated embryonic day 14 thymus lobes expressed the surface molecules I‐A and H‐2D, whereas these cells in embryonic day 12 thymus lobes were negative for these surface molecules. Thus, our findings suggest that the embryonic day 12 thymus lobe contains T cell precursors, but that the undeveloped thymic stromal cells are insufficient to support full T cell development.
The non‐histone chromosomal protein HMG‐I(Y) contributes to repression of the immunoglobulin heavy chain germ‐line ε RNA promoter
Authors: Kim Jinny , Reeves Ray , Rothman Paul , Boothby Mark 
Published: March 2007

AbstractThe rate of germ‐line RNA transcription correlates with the rate of immunoglobulin heavy chain isotype switching. A promoter element for the transcription of RNA from the germ‐line mouse immunoglobulin ε heavy chain constant region gene is induced by interleukin(IL)‐4 and lipopolysaccharide, and is bound at its transcription initiation sites by an IL‐4‐inducible nuclear protein, NF‐BRE. To examine the function of the binding site for this IL‐4‐inducible complex, substitution mutations were introduced in the promoter. These binding site mutations increased promoter activity and decreased binding of NF‐BRE. To investigate the paradox of an IL‐4‐inducible protein binding to a repressor site in an IL‐4‐inducible promoter, we determined that the non‐histone chromosomal protein HMG‐I(Y) binds at the transcription initiation sites of the germ‐line epsilon promoter. Assays with antisera against HMG‐I(Y) revealed monomeric HMG‐I(Y) in nuclear extracts. Cotransfection of an expression construct directing the synthesis of anti‐sense HMG‐I(Y) RNA also increased promoter activity, consistent with a repressor function of HMG‐I(Y). Thus, the data are most consistent with a model in which HMG‐I(Y) participates in repression of promoter activity. The effects of IL‐4 may include derepression at this site.
Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia
Authors: De La Morena Maite , Haire Robert N. , Ohta Yuko , Nelson Robert P. , Litman Ronda T. , Day Noorbibi K. , Good Robert A. , Litman Gary W. 
Published: March 2007

AbstractThe transcription pattern of the heavy chain immunoglobulin gene locus was analyzed in a 6‐month‐old female with agammaglobulinemia characterized by the absence of mature B cells in peripheral blood, arrested B cell development in the bone marrow and lack of germinal center development. DNA sequencing provided no evidence of mutations within the coding region of the Bruton's tyrosine kinase gene. Polymerase chain reaction‐generated cDNA libraries from blood and bone marrow were screened initially using JH and CH oligodeoxynucleotide probes and VH family‐specific probes. Only 10% of the transcripts constituted mature VDJCμ recombinations. Ninety percent of the cDNA were sterile immunoglobulin transcripts comprised of: DJCμ (DH−JHCμ), JCμ (JH−Cμ), ECμ (enhancer spliced to Cμ), SCμ and ICμ [corresponding to switch (S) and intron (I) regions spliced to Cμ]. In the mature immunoglobulin transcripts, VH use indicated germline expression with little evidence of somatic mutation. All cDNA were of the Cμ type. Different D segments, D‐D joining events and unknown D‐like elements were noted in the DJCμ and VDJCμ transcripts. This pattern of immunoglobulin rearrangements, along with the phenotypic cell surface antigen characteristics (CD19−), suggest that an earlier arrest in B cell development than is characteristic of Bruton's X‐linked agammaglobulinemia has occurred in this patient.
Specific hyporesponsiveness of alloreactive peripheral T cells induced by CD4 antibodies
Authors: Vincent Claude , Fournel Sylvie , Wijdenes John , Revillard Jean‐Pierre 
Published: March 2007

AbstractWe investigated whether exposure of naive and in vitro pre‐activated T cells to CD4 monoclonal antibodies (mAb) could induce specific hyporesponsiveness to a subsequent challenge in the absence of CD4 mAb. Unfractionated peripheral blood mononuclear cells were cultured with mitomycin‐treated B cell lines as stimulator cells, in the presence or absence of CD4 mAb, then challenged with the same or unrelated stimulator cells. The kinetics of [3H] thymidine incorporation, blast transformation and CD25 expression were determined. Cells activated in primary or secondary culture in the presence of CD4 mAb demonstrated a markedly decreased response to subsequent challenge in the absence of antibody. This effect was reproduced with three different CD4 mAb of the IgG1 and IgG2a subclasses, which recognize two distinct epitopes of the CD4 molecule. Addition of recombinant interleukin‐2 (rIL‐2) during exposure to CD4 mAb failed to prevent the induction of specific hyporesponsiveness. Similarly, exogenous rIL‐2, added together with stimulating cells, failed to restore the specific proliferative response, indicating that the mechanisms were different from those of classical anergy. The hyporesponsiveness was clonally restricted since CD4 mAb‐pretreated cells developed a normal primary response to third‐party stimulator cells. No increase in the percentage of apoptotic cells was observed in hyporesponsive cell populations, but selective clonal deletion cannot be excluded. The data demonstrate a delayed effect of CD4 ligation on T cell responses to a subsequent challenge.
Interleukin‐12 profoundly up‐regulates the synthesis of antigen‐specific complement‐fixing IgG2a, IgG2b and IgG3 antibody subclasses in vivo
Authors: Germann Tieno , Bongartz Martina , Dlugonska Henryka , Hess Henry , Schmitt Edgar , Kolbe Ludger , Kölsch Eckehart , Podlaski Frank J. , Gately Maurice K. , Rüde Erwin 
Published: March 2007

AbstractThe influence of the cytokine interleukin‐12 (IL‐12) on humoral immune responses was studied in vivo. CBA/J mice immunized with protein antigens (keyhole limpet hemocyanin, phospholipase A2) adsorbed to aluminum hydroxide (Alum) develop a Th2‐like immune response characterized by the production of large amounts of IgG1 as well as some IgE but little IgG2a, IgG2b and IgG3 antibodies. IL‐12 is a cytokine that promotes the development and the activation of Th1 cells. Th1 cells are involved in the induction of cellular immunity, which is characterized by low or absent antibody production. On the other hand, some Th1‐like immune responses are associated with a strong antibody production of the IgG2a, IgG2b and IgG3 subclasses. Thus, we investigated whether treatment with IL‐12 would down‐regulate the humoral immune response or stimulate antibody production of the IgG2a, IgG2b and IgG3 subclasses. We observed that: 1) administration of IL‐12 to mice together with protein antigens adsorbed to Alum strongly enhanced the humoral immune response by increasing the synthesis of antigen‐specific antibodies of the IgG2a, IgG2b and IgG3 subclasses 10‐ to 1000‐fold. The synthesis of IgG1 was not or only slightly (2–5‐fold) enhanced, whereas that of the IgE isotype was suppressed. 2) These effects of IL‐12 were observed when high (10 μg, 100 μg) or low doses (0.1 μg) of antigen were used for immunization. 3) Titration of IL‐12 in vitro revealed that IgG2a is strongly up‐regulated over a wide dose range of IL‐12 (10 to 1000 ng/day). 4) The effects of IL‐12 in vivo are at least partially interferon (IFN)‐γ‐dependent because an anti‐IFN‐γ mAb in combination with IL‐12 prevented most of the enhanced IgG2a production. 5) Mice receiving IL‐12 showed a strong up‐regulation of IFN‐γ but no inhibition of IL‐5 synthesis by spleen cells activated ex vivo with antigen. These results suggest that IL‐12 is a potent adjuvant for enhancing humoral immunity to protein antigens adsorbed to Alum, primarily by inducing the synthesis of the complement‐fixing IgG subclasses 2a, 2b and 3.
Assessment of a functional role of auto‐anti‐idiotypes in idiotype dominance
Authors: Ismaili Jamila , Brait Maryse , Leo Oberdan , Urbain Jacques 
Published: March 2007

AbstractWe have used a well‐defined idiotypic system, the cross‐reactive idiotype of A strain (CRIA) (Ab1) idiotype generated in A/J mice injected with arsonate coupled to keyhole limpet hemocyanin (ARS‐KLH), to determine the frequency of precursors for auto‐anti‐idiotypic antibodies (auto‐Ab2) in naive and immunized A/J mice by limiting dilution analysis after polyclonal activation by lipopolysaccharide. In naive animals, the precursor frequencies of auto‐Ab2 B cells were below the limit of sensitivity of the technique in the majority of A/J mice, and could be detected in only 20% of the animals. Upon immunization with ARS‐KLH, a large increase in auto‐Ab2 precursor frequency was observed. This shift in frequency was not found when A/J mice were injected with KLH alone, or when BALB/c mice, which do not express the CRIA idiotype, were injected with ARS‐KLH. To study the functional role of the auto‐Ab2 B cells, we injected neonatal A/J mice with polyclonal rabbit Ab3 antibodies directed against a recurrent idiotype of auto‐Ab2. Thereafter, these mice were injected with ARS‐KLH. Although the anti‐arsonate response level was normal, the CRIA Ab1 expression was reduced tenfold. Thus, the suppression of auto‐Ab2 affects Ab1 dominance. We further show that the presence of maternal Ab1 can strongly modify the immune response of the offspring by inducing higher levels of the idiotype after immunization. Furthermore, IgM anti‐arsonate antibodies were detected before immunization with antigen. From these data, we conclude that the affinity of antigen alone cannot explain the dominance of CRIA. Network selection is important in the shaping of the available repertoire.
Recognition of E‐cadherin on epithelial cells by the mucosal T cell integrin αM290β7 (αEβ7)
Authors: Karecla Paula I. , Bowden Simon J. , Green Sally J. , Kilshaw Peter J. 
Published: March 2007

AbstractThe integrin αM290β7 on the surface of a T cell hybridoma, MTC‐1, mediated adhesion of these cells to the mouse epithelial cell line CMT93. This interaction was critically dependent on the presence of divalent cations; Mn2+ strongly promoted adhesion, Ca2+ was ineffective and Mg2+ gave intermediate results. Antibodies to molecules on the surface of CMT93 cells were tested for inhibition of adhesion. One monoclonal antibody (mAb) against E‐cadherin, ECCD‐2, was found to have significant inhibitory activity. Other mAb to E‐cadherin and antibodies to other molecules had no effect. To show that inhibition by ECCD‐2 was specific for adhesion mediated by αM290β7, MTC‐1 cells were induced to adhere to CMT93 via the LFA‐1/ICAM‐1 pathway. For this purpose, the epithelial cells were treated with interferon‐γ and tumor necrosis factor‐α to induce ICAM‐1 expression and, in addition, αM290β7 on MTC‐1 cells was down‐regulated by culturing the cells in the absence of transforming growth factor β. Under these circumstances adhesion of MTC‐1 cells to CMT93 was inhibited by an antibody to LFA‐1 but not by ECCD‐2. Transfection of mouse L cells with cDNA for mouse E‐cadherin enabled MTC‐1 cells to adhere to them through the αM290β7 integrin; this interaction was inhibited both by ECCD‐2 and by blocking antibody against the integrin. These data strongly suggest that E‐cadherin is a principal ligand for αM290β7.
CD40 ligand is functionally expressed on human eosinophils
Authors: Gauchat Jean‐François , Henchoz Sybille , Fattah Dilnya , Mazzei Gonzalo , Aubry Jean‐Pierre , Jomotte Therese , Dash Laura , Page Kevin , Solari Roberto , Aldebert Delphine , Capron Monique , Dahinden Clemens , Bonnefoy Jean‐Yves 
Published: March 2007

AbstractCD40 ligand (CD40L), a surface molecule which can be expressed by T cells, mast cells and basophils, has been shown to be involved in the control of B cell proliferation, immunoglobulin class switching as well as in the activation of monocytes and T cells. We demonstrate that CD40L can also be expressed constitutively by eosinophils from an hypereosinophilic patient or, upon activation, by the eosinophilic cell line EOL‐3 and normal blood eosinophils. Eosinophils were able to induce, in conjunction with IL‐4, CD40L‐dependent B cell proliferation in vitro. These results suggest that CD40L could play a role in the inflammatory processes during which eosinophil infiltration and activation are observed.
More newly formed T than B lymphocytes leave the intestinal mucosa via lymphatics
Authors: Rothkötter Hermann J. , Hriesik Claudia , Pabst Reinhard 
Published: March 2007

AbstractMany lymphocytes are produced in the intestinal mucosa, especially in the Peyer's patches. These newly formed lymphoid cells leave the gut wall, undergo further maturation and many reach the lamina propria of the intestinal mucosa where they function as effector and regulator cells of the intestinal immune response. However, the number and subset composition of these wall are not known. Therefore, the intestinal lymph duct was cannulated in eight minipigs, in which the mesenteric lymph nodes had been removed 3 months earlier. Thus, it was possible to obtain all lymphocytes leaving the intestinal mucosa including the Peyer's patches via lymphatics. The hourly output of lymphocyte subsets was examined over the course of 93 h. The percentage and the absolute numbers of newly formed T cells (CD2+, CD8+) and B cells (IgA+, IgM+) were determined by examining the incorporation of the DNA precursor bromodeoxyuridine. After a single i.v. bromodeoxyuridine injection 8.5% of the T, 55% of the IgA+ and 25% of the IgM+ cells were labeled. In absolute numbers (1.9 ± 0.7) × 106 newly formed T cells, (0.4 ± 0.3) × 106 IgA+ cells and (0.5 ± 0.4) × 106 IgM+ cells emigrated from the gut wall per hour. Both T and B lymphocyte subpopulations that are produced in the intestinal mucosa leave the gut wall via lymphatics; interestingly, the T cells outnumber the B cells. Obviously the induction and maintenance of mucosal immunity depend to a large extent on the function of newly formed T lymphocytes emigrating from the Peyer's patches and/or from the mucosa without Peyer's patches.
Gene structure and chromosomal localization of the mouse homologue of rat OX40 protein
Authors: Birkeland Marian L. , Copeland Neal G. , Gilbert Debra J. , Jenkins Nancy A. , Barclay A. Neil 
Published: March 2007

AbstractThe OX40 protein is expressed only on activated rat CD4+ T blasts and is a member of a superfamily of cell surface molecules which includes CD40, CD30, CD95 (Fas), CD27, 4‐1BB antigens and the receptors for tumor necrosis factor (TNF) and nerve growth factor (NGF). The proteins of this group are related to each other by having three to six repeats of a cysteine‐rich sequence in their extracellular domains. Members of this family of receptors have also been shown to bind to ligands which are structurally related to TNF.The mouse homologue of the rat OX40 protein was cloned at the cDNA and genomic levels. The gene structure shows that there are several intron/exon borders shared between OX40 and CD27, CD40, TNF receptor type I, CD95 and 4‐1BB genes. This group of genes is less closely related structurally to the gene structure of the NGF receptor. The gene encoding murine OX40 has been placed on mouse chromosome 4, in an area which contains the genes for TNF receptor type II and 4‐1BB, and is syntenic with a region of human chromosome 1 which contains human TNF receptor type II, OX40, and CD30 genes.
Induction in mice of serum IgE levels after treatment with anti‐mouse IgD antibodies is preceded by differential modulation of tissue cytokine gene transcription
Authors: Kricek Franz , Ruf Christine , Žunić Melita , De Jong Gerard , Dukor Peter , Bahr George M. 
Published: March 2007

AbstractInjection of mice with purified goat anti‐mouse IgD (GAMD) leads to an interleukin (IL)‐4‐dependent increase of serum IgE levels. Challenge of GAMD‐primed mice with goat IgG (GIG) initiates a secondary immune response with elevated serum IgE. In this report, kinetic cytokine transcript profiles of murine lymphoid tissues in response to primary i.v. GAMD treatment, as well as GIG challenge are presented. For the first time, gene transcription patterns of the recently described cytokines IL‐12 and IL‐13 are shown and compared with the corresponding patterns for other cytokine genes involved in IgE regulation, i.e. IL‐4, and interferon (IFN)‐γ. After GAMD injection, two groups of induction profiles were observed in spleen, mesenteric lymph nodes and Peyer's patches: while IL‐4 and IL‐12p35 gene transcription was strongly enhanced, IFN‐γ, IL‐12p40 and IL‐13 mRNA were only moderately induced. Generally, maximal mRNA induction was measured on days 3 to 4 after GAMD treatment. The data demonstrate a clear‐cut difference between the IL‐4 and IL‐13 response on the transcriptional level although both gene products show similar biological activities. The cytokine mRNA profiles support the assumption of IL‐4 playing the central role in generating an IgE response. However, they do not reflect a strict Th1 versus Th2 cytokine gene transcription pattern but rather point towards a concerted action of various, partially antagonizing cytokines with respect to the regulation of IgE synthesis. IL‐12 may, possibly via stimulation of IFN‐γ synthesis, represent a counterbalancing factor in the IL‐4‐mediated IgE response.
Surface expression of β2‐microglobulin‐associated thymus‐leukemia antigen is independent of TAP2
Authors: Rodgers John R. , Mehta Vidya , Cook Richard G. 
Published: March 2007

AbstractMouse thymus‐leukemia antigen (TL), like other major histocompatibility complex (MHC) class I‐b antigens, displays signs of a specialized function. It is normally expressed at high levels on immature thymocytes and at moderate levels on gut epithelium and activated mature T cells. A promoter/enhancer region unique among class I genes accounts for this narrow range of tissue distribution. Like most other class I molecules, TL is dependent upon endogenous β2‐microglobulin (β2m) for transport to the surface. However, here we show that unlike most other MHC class I molecules, TL is expressed efficiently in the absence of functional transporter associated with antigen processing subunit 2 (TAP2). A putative fourth TLa gene cloned from A.SL1 cells was expressed in RMA and RMA‐S cells. In bulk transformants, TL expression is higher in TAP2− RMA‐S cells than in wild‐type RMA cells, and is not elevated by incubation at reduced temperatures or exposure to exogenous β2m. Analysis of immunoprecipitasted molecules by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicates that TL is processed normally in RMA‐S cells and is associated with β2m both intracellularly and at the cell surface. However, TL heavy chains expressed on the cell surface in the absence of TAP2 are cleaved to a predominant 38 kDa fragment, presumably the result of an altered conformation that renders TL more susceptible to proteolysis. These results suggest that while TL may normally acquire TAP2‐dependent peptides, this class I‐b molecule does not require them for efficient export to, and stable expression at the cell surface.
Antibody response against poly (Glu60Ala30Tyr10) terpolymer and bacterial levan in ϰ‐deficient mice
Authors: Pricop Luminita , Hatakeyama Akira , Moran Tom , Bona Constantin 
Published: March 2007

AbstractIn murine species, the ϰ+‐bearing immunoglobulins‐dominate the antibody (Ab) repertoire with a ϰ/λ ratio of 95 : 5. The aim of the present study is to investigate the characteristics of the antibody response in ϰ‐deficient (K −/−) mice immunized with a T‐dependent synthetic antigen, poly (Glu60Ala30Tyr10) (GAT) and a T‐independent antigen, bacterial levan (BL). K −/− mice were obtained by targeted deletion of the JϰCϰ gene segments. In response to GAT, K −/− mice respond by producing increasing amounts of anti‐GAT Igλ1 and Igλ2 in the primary as well as secondary response, although anti‐GAT specific monoclonal antibodies (mAb) raised in K −/− mice are mostly of IgM isotype. The GAT public idiotype, GATIdX, present on all GAT‐specific Ab bearing x light chain, is not detected in the sera of K −/− mice or on any of the anti‐GATλ1 mAb. In response to BL, the amount of Igϰ1+ Ab in K −/− mice is comparable to the amount of Igϰ+ Ab in normal mice. However, λ2+ Ab are detected neither in wild‐type nor in K −/− mice. Like ϰ+ Ab, the majority of λ1+ mAb are specific for β2–6 fructosan present in BL and rye levan and, to some extent, express the BL‐specific idiotype, A48ld. Our results show that important compensatory mechanisms occur in ϰ‐deficient mice, restoring their ability to mount immune responses against a variety of T‐dependent and T‐independent antigens by the alternative usage of the clonally restricted λ repertoire.