bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of immature thymocytes: initiation of CD3, CD4, and CD8 acquisition parallels down‐regulation of the interleukin 2 receptor α chain
Authors: Petrie Howard T. , Pearse Martin , Scollay Roland , Shortman Ken 
Published: March 2007

AbstractWe have previously identified a developmental sequence among immature thymocytes, prior to their expression of the lineage markers CD3, CD4, and CD8. This sequence is marked by transient expression of the interleukin 2 receptor α chain (IL 2Rα). The most mature cells in this sequence (surface phenotype heat‐stable antigen (HSA)++ Pgp‐1− IL 2Rα−) are the immediate precursors to CD4+CD8+ small cortical thymocytes, and have by definition been considered to be CD4−CD8−. We now show that these cells display low levels of surface CD4 and CD8, but not CD3. This low‐level expression begins to appear immediately after the loss of IL 2Rα expression. Northern blot analysis for mRNA expression confirms that these IL 2Rα− cells are transcribing CD4 and CD8 mRNA, in contrast to their immediate (IL 2Rα+) precursor. Upon unstimulated culture, these IL 2Rα− cells gradually acquire high levels of CD4 and CD8, as well as low levels of CD3, whereas IL 2Rα− cells do not. These findings suggest that the IL 2Rα+ subset is the end of the true CD3−CD4−CD8− phase, and that the intracellular signals for CD3, CD4, and CD8 acquisition occur simultaneously with, or immediately prior to, the signal for down‐regulation of IL 2Rα.
T helper cell epitope of rabies virus nucleoprotein defined by tri‐ and tetrapeptides
Authors: Ertl Hildegund C. J. , Dietzschold Bernhard , Otvos Laszlo 
Published: March 2007

AbstractT cell clones and subsequently hybridomas were generated from rabies virus‐immune C3H/He mice to an immunodominant epitope of the viral nucleoprotein, termed 31D, that had previously been identified by a 15‐amino acid‐long synthetic peptide. T cells to this epitope that by phenotypical and functional characteristics belonged to the T helper cell subset were shown to respond to most rabies and rabies‐related viruses. In order to define the minimal sequence needed to elicit a response from 31D‐specific T cell clones or hybridomas, a number of peptides of varied lengths, i.e. 3–32 amino acids long, were tested. The ability of the peptides to induce a response was inversely correlated in their lengths, i.e., short peptides (3–5 amino acids long) had to be used at 106 times higher concentrations as compared to long peptides (15 or 32 amino acids long). Conversely, the specificity of the T cell response was directly correlated to the length of the peptides, i.e., while the response to 15‐amino acid‐long peptides exhibited a high degree of specificity, the response to 3‐ to 5‐amino acid‐long peptides showed a high degree of flexibility. The long as well as the short peptides had to be presented in association with I‐Ek. We speculate that in this system the T cell receptor interacts predominantly with a peptide‐induced modification of the I‐Ek molecule.
Differential expression of the alternatively spliced exons of murine CD45 in Th1 and Th2 cell clones
Authors: Luqman Mohammad , Johnson Pauline , Trowbridge Ian , Bottomly Kim 
Published: March 2007

AbstractAntigen‐specific murine CD4+ T cell clones can be divided into functionally distinct subsets known as Th1 and Th2. To date these cells have been indistinguishable by surface phenotype. This report identifies two anti‐CD45R monoclonal antibodies (14.8 and C363.16A) that bind preferentially to Th2 cells. Further analysis of the CD45‐specific mRNA in Th1 and Th2 cells shows clear differences between these two cell types. Th1 cell clones express mRNA for the two smallest forms of CD45 containing none or only one of the alternatively splices exons. In contrast, Th2 cell clones express predominantly the high molecular weight isoforms of CD45 containing two or three of the alternatively spliced exons.
Specific suppression of antibody responses by soluble protein‐specific, class II‐restricted cytolytic T lymphocyte clones
Authors: Shinohara Nobukata , Huang Yi‐Ying , Muroyama Akiko 
Published: March 2007

AbstractAntigenic stimulation with exogenous soluble proteins induces cytotoxic T lymphocytes (CTL) recognizing antigenic peptides presented on class II major histocompatibility complex (MHC) molecules. Such CTL have been shown to lyse preferentially B cells expressing immunoglobulin receptors reactive with the relevant antigens, presumably because such B cells can efficiently trap and present the antigen. Therefore, possible involvement of soluble protein antigen‐specific CTL in specific suppression of antibody responses has been hypothesised. In this report, keyhole limpet hemocyanin and ovalbumin‐specific, class II‐restricted CD4+ CTL clones established from lymph nodes of immunized mice were examined for their suppressive activities on antibody production. When these CTL clones were added to in vitro secondary cultures, genetically restricted, carrier‐specific suppression of anti‐2, 4, 6‐trinitrophenyl antibody production was observed. These data therefore demonstrate that CTL directed toward soluble antigens are capable of mediating specific suppression of antibody responses. Furthermore, the antibody response of MHC‐heterozygous F1 lymphocytes was almost completely suppressed by a CTL clone restricted to one parental class II MHC antigen, indicating that the mechanism of suppression by these CTL is distinct from that by classical suppressor T cells.
Role of bone marrow cells in autoantibody production and lymphoproliferation in the novel mutant strain of mice, CBA/KIJms‐lprcg/lprcg
Authors: Kimura Mikio , Katagiri Takuya , Kikuchi Yoshimi , Shimada Kaoru , Nariuchi Hideo , Wakabayashi Tomo , Matsuzawa Akio 
Published: March 2007

AbstractThe novel mutant gene, lprcg, is allelic with lpr, but complements the gld gene in induction of lymphoproliferation. Mice with this autosomal recessive mutation, CBA/KlJms‐lprcg/lprcg (CBA‐lprcg), served in this study to analyze the abnormalities of bone marrow (BM) stem cells responsible for autoantibody production and lymphoproliferation by BM transfer experiments. Transferred CBA‐lprcg BM cells might have differentiated into so‐called double‐negative, anomalous lymphoid cells and caused production of autoantibodies such as anti‐DNA antibodies in the environment of normal CBA/KlJms−+/+ (CBA−+) mice. Macroscopic graft‐vs.‐host‐like disease as reported in lpr→non‐lpr BM transfer was not observed in these recipients. In this BM chimera, however, lymphoproliferation did not ensue and the host's lymph nodes became atrophic. The lymphoproliferation required the coexistence of lprcg BM cells and lprcg lymph nodes in CBA−+ mice. The results indicate that the functions of the lprcg gene are expressed at both BM and lymph node levels. Thus, this mutant strain of mice should provide an excellent model for analyzing aberrant lymphocyte differentiation from the BM cells leading to autoimmunity and lymphoproliferative disorder.
Prevention of lethal graft‐vs.‐host disease by a single low dose injection of anti‐T cell monoclonal antibody to the allograft recipients
Authors: Knulst André C. , Bril‐Bazuin Clara , Benner Robbert 
Published: March 2007

AbstractWe investigated the capacity of monoclonal antibody (mAb) treatment to prevent graft‐vs.‐host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice, employing anti‐T cell (subset) mAb and a fully allogeneic strain combination. In this strain combination, purified CD4+ cells were able to induce a lethal GVH reaction, whereas purified CD8+ cells were not. In the same strain combination, a single intraperitoneal injection of IgG2b anti‐Thy‐1 mAb, one day after reconstitution, caused a dose‐dependent improvement of the survival. A single injection of a dose as low as 12.5 μg per mouse was already effective. Intravenous and intraperitoneal administration of the mAb appeared equally effective. For effective prevention of GVHD the treatment could be postponed until the 4th day after transplantation, but treatment delayed until day 6 was no longer effective. Treatment with IgG2b mAb specific for either helper or cytotoxic T cells also led to improvement of GVHD and survival, but was less effective than treatment with anti‐Thy‐1 mAb. Clinically, there was a difference in the effectiveness of anti‐CD4 and anti‐CD8 treatment, since symptoms of GVHD started earlier in the anti‐CD8 treated group and the survival was better in the anti‐CD4 treated group. These results press for prospective clinical studies employing anti‐T cell mAb treatment early after allogeneic bone marrow transplantation, especially in HLA mismatched cases.
A monoclonal antibody specific for a cytochrome c T cell stimulatory peptide inhibits T cell responses and affects the way the peptide associates with antigen‐presenting cells
Authors: Jemmerson Ronald , Johnson Julia G. , Burrell Edwin , Taylor P. Sean , Jenkins Marc K. 
Published: March 2007

AbstractA monoclonal antibody (mAb) specific for the 93–104 segment of pigeon cytochrome c (cyt) was shown to block interleukin 2 production and proliferation by pigeon cyt‐specific T cells in response to the pigeon cyt 81–104 peptide using either the LK35.2 B cell hybridoma or normal splenocytes as antigen‐presenting cells (APC). The mAb inhibited the response to soluble peptide antigen presented by metabolically inactive paraformaldehyde‐fixed APC but not the response to APC that were pre‐pulsed with Ag. These results suggest that the mAb blocked the formation of peptide‐major histocompatibility complex (MHC) class II molecule complexes at the cell surface but did not displace the peptide once bound to the MHC class II molecule. As determined by direct binding experiments using labeled peptide, the major means of free peptide association with live APC was fluid‐phase endocytosis. No free peptide associated directly with the MHC class II molecule at the cell surface near 0°C since APC pulsed with peptide on ice did not activate cyt‐specific T cells. The mAb enhanced the association of the radiolabeled peptide with APC at 4°C apparently by binding of the peptide‐mAb complex to Fc receptors. By stripping molecules from the LK35.2 cell surface using a nonspecific protease it was shown that the peptide‐mAb complexes were not internalized either at 4°C or 37°C. Since the mAb was found to stably bind the peptide at pH levels below that of endosomes (pH 5.5–6.2) even if the peptide‐mAb complexes were taken up by fluid‐phase endocytosis, it is likely that the peptide would not be able to associate with MHC class II molecules inside the APC. This mAb appears to inhibit T cell activation by blocking the formation of peptide‐MHC class II molecule complexes at the cell surface and by interfering with uptake of the peptide into endosomes. Therefore, it is different from other antibodies that have been reported to block T cell receptor recognition of preformed peptide/MHC class II molecule complexes.
Cell‐type‐specific recognition of allogeneic cells by alloreactive cytotoxic T cells: A consequence of peptide‐dependent allorecognition
Authors: Heath William R. , Sherman Linda A. 
Published: March 2007

AbstractRecently, we provided the first direct evidence that the determinant recognized by some alloreactive cytotoxic T lymphocytes (CTL) clones included an endogenous peptide antigen(s), which could be derived by cyanogen bromide cleavage of cytoplasmic proteins. The studies outlined in this report provide three important findings which confirm and extend our previous results. First, the description of peptide‐dependent Kb‐specific alloreactive CTL clones is now extended to clones isolated from several responders primed with allogeneic EL4 tumor cells. This indicates that the previously reported results were not unique to the original EL4‐primed responder. Second, we establish that peptide‐dependent Kb‐specific alloreactive CTL clones can be identified after priming with normal allogeneic spleen cells. Thus, induction of peptide‐dependent CTL clones is not a unique property of EL4 tumor cells. These results suggest that peptide plays an important role in formation of the allogeneic determinants recognized during graft rejection. Third, these studies reveal that a number of alloreactive CTL clones exhibit cell‐type‐specific recognition of allogeneic murine target cells. This is consistant with the possibility that some CTL clones recognize peptide antigens that are limited in their tissue distribution. The mechanisms and implications of these findings are discussed.
Cross‐linking of VLA/CD29 molecule has a co‐mitogenic effect with anti‐CD3 on CD4 cell activation in serum‐free culture system
Authors: Yamada Akira , Nojima Yoshihisa , Sugita Kanji , Dang Nam H. , Schlossman Stuart F. , Morimoto Chikao 
Published: March 2007

AbstractIn this study, we demonstrated that antibodies reactive with a common β1 subunit (CD29) of the VLA family of antigens could synergize with CD3 but not CD2 in inducing CD4 cell proliferation in a serum‐free culture system. The extent of activation was similar to that obtained when CD4 cells were cultured with anti‐CD3 plus fibronectin. The proliferative response induced via the CD3‐CD29 pathway was associated with the interleukin (IL) 2 autocrine pathway, including IL2 production and IL2 receptor expression. Specifically, cross‐linking of VLA‐5, but not other members of the VLA family of antigens with the CD3 molecule induced strong CD4 cell activation. However, cross‐linking of CD3 with other cell surface antigens such as CD4 did not induce CD4 cell activation in this serum‐free culture system. The above results strongly suggest that the VLA/CD29 family of antigens may play an important role in regulating CD4 T cell activation via the CD3‐T cell receptor pathway.
Selective migration of the human helper‐inducer memory T cell subset: confirmation by in vivo cellular kinetic studies
Authors: Pitzalis Costantino , Kingsley Gabrielle H. , Covelli Michele , Meliconi Riccardo , Markey Andrew , Panayi Gabriel S. 
Published: March 2007

AbstractThe vast majority of T cells present in chronic inflammatory lesions are of the helper‐inducer/memory (CD45RO+CD29+) phenotype; suppressor‐inducer/naive cells (CD45RA+) are virtually absent. Furthermore, CD4+ T cells are found more frequently than CD8+ cells. Previous in vitro studies have suggested that this may be, in part, due to the increased capacity of CD45RO+CD29+ T cells to bind to endothelium and, thus, enter inflammatory foci but no in vivo evidence for preferential migration exists. To investigate this, suction blisters were generated over a purified protein derivative of tuberculin‐induced delayed‐type hypersensitivity lesions in humans and the phenotype of the blister cells was studied. At all time points, a preponderance of CD45RO+CD29+ cells over CD45RA+ cells and of CD4 over CD8 cells was demonstrated. Because of the rapid kinetics, this appears to represent preferential migration of these cell types rather than in situ proliferation or phenotype conversion. In addition the expression of the CD45RO but not the CD45RA antigen was up‐regulated on blister T cells compared to blood T cells. Analysis of blister fluid showed high concentrations of interleukin 6 but not tumor necrosis factor‐α or lymphotoxin. This study shows for the first time directly in vivo that CD45RO+ T cells migrate preferentially into inflammatory lesions. Furthermore, it illustrates the potential usefulness of this system in the analysis of the early phases of the immune inflammatory response.
Human transferrin allows efficient IgE production by anti‐CD3‐stimulated human lymphocytes at low cell densities
Authors: van der Pouw‐Kraan Tineke , van Kooten Cees , van Oers Rien , Aarden Lucien A. 
Published: March 2007

AbstractA solid‐phase‐coupled anti‐CD3 T cell activation system was used to study the regulation of human IgE production in vitro. Using 5000 peripheral blood lymphocytes from healthy donors, containing 10%–20% B lymphocytes and no monocytes, IgE was produced very efficiently on a per cell basis. A key observation was that apart from interleukin (IL)4, human transferrin was essential for IgE production. Furthermore it was found that IgE was produced at low densities only; at higher cell concentrations IgE production was completely abrogated, whereas IgM production increased with increasing cell density. This inhibition at higher cell densities is probably mediated by IL 2. Addition of low amounts (6 U/ml) of IL 2 strongly enhanced IgE and IgM production at low cell densities, but higher concentrations of IL 2 (50 U/ml) were strongly inhibitory for IgE production.
FcγRIII (CD16) on human macrophages is a functional product of the FcγRIII‐2 gene
Authors: Perussia Bice , Ravetch Jeffrey V. 
Published: March 2007

AbstractThe low‐affinity Fc receptor for immune‐complexed IgG (FcγRIII; CD16) present on in vitro cultured human monocytes are encoded by an FcγRIII‐2 gene that, by cDNA sequence analysis, is identical to that expressed on tissue macrophages and on natural killer cells. In macrophages, FcγRIII‐2 encodes a glycoprotein of 52‐62 kDa, with a peptide backbone of 33 kDa identical to that of the homologous receptor on natural killer cells. Like this and unlike in polymorphonuclear neutrophils, FcγRIII (CD16) on cultured monocytes is insensitive to phosphatidylinositol‐specific phospholipase C, is not allelic for the neutrophil NA alloantigens NA‐1/NA‐2, is not recognized by a monoclonal antibody (1D3) detecting an epitope present only on neutrophil FcγRIII (CD16) and functions to trigger cytotoxicity upon ligand binding.
Regulation of tumor necrosis factor (TNF) release by murine peritoneal macrophages: role of cell stimulation and specific phagocytic plasma membrane receptors
Authors: Stein Michael , Gordon Siamon 
Published: March 2007

AbstractIn spite of the physiologic and pathologic importance of tumor necrosis factor (TNF), the cellular factors that govern its release by macrophages (MΦ) are poorly understood, in comparison with other secretory products. We have studied the role of MΦ heterogeneity and of plasma membrane receptors in regulating TNF release in vitro. Resident and various exudate murine peritoneal MΦ populations were challenged with lipopolysaccharide (LPS) or different phagocytic particles, and TNF release assayed by cytotoxicity for L‐929 fibroblasts. Resident peritoneal MΦ (RPMΦ) released a small amount of TNF in response to LPS whereas thioglycollate‐elicited MΦ (TPMΦ) released high levels of TNF (5000 U/3 × 105 MΦ/ml). MΦ elicited by Bio‐Gel polyacrylamide beads (BgPMΦ), another nonspecific inflammatory stimulus, or early in the course of intraperitoneal Bacillus Calmette‐Guérin infection, before recruited cells become immunologically activated, released tenfold less TNF after the same stimulus. By contrast, TNF release in response to various phagocytic triggers was similar (∼300‐600 U/3 × 105 MΦ/ml) in all MΦ populations including RPMΦ. The response by BgPMΦ to LPS was enhanced by pre‐treatment in vitro with interferon‐γ or thioglycollate broth.With respect to phagocytic receptor triggering we found that complement receptor type 3 (CR3) ligation or latex uptake did not mediate release of significant quantities of TNF (<48 U/3 × 105 MΦ/ml) by any MΦ, whereas ligation of the Fc receptor for IgG1/IgG2b subclasses or of receptors for zymosan particles sufficed, in the absence of ingestion. to induce release of circa 500 U/3 × 105 MΦ/ml TNF by all MΦ tested. Our studies show that MΦ vary in respect to priming for TNF release and that heterogeneity should be related to a particular triggering stimulus. Furthermore, the capacity of some MΦ populations to release unusually high levels of TNF depends on immune or nonspecific stimuli subsequent to the process of inflammatory recruitment.
The effect of the immunosuppressant FK‐506 on alternate pathways of T cell activation
Authors: Bierer Barbara E. , Schreiber Stuart L. , Burakoff Steven J. 
Published: March 2007

AbstractStructurally unrelated, FK‐506 and cyclosporin (CsA) bind to and inhibit the action of distinct cytoplasmic receptors, FK‐506‐binding protein (FKBP) and cyclophilin (CyP), respectively. These receptors, termed immunophilins, share no sequence similarity, and yet both have been demonstrated to be capable of catalyzing the cis‐trans isomerization of peptidyl‐prolyl bonds (rotamase activity). Because FK‐506 and CsA bind to different intracellular target structures, we investigated the spectrum of action of FK‐506, in comparison to CsA, on T cell activation. We have shown that FK‐506, like CsA, is able to inhibit T cell activation mediated not only by the T cell receptor‐CD3 complex, but also via another surface molecule, CD2. T cell proliferation, stimulation of interleukin 2 production, and induction of apoptosis were all sensitive to inhibition by both FK‐506 and CsA. With each parameter of activation, FK‐506 is approximately 10‐100‐fold more effective than CsA. In contrast, FK‐506 did not affect T cell proliferation induced by anti‐CD28 monoclonal antibody in the presence of phorbol 12‐myristate 13‐acetate. This CD28 pathway, however, was inhibitable by a structural homolog of FK‐506, rapamycin, demonstrating that the mechanism of action of FK‐506 has specificity. These data suggest that immunophilins or the complex of drug coupled to immunophilin (i.e. FK‐506/FKBP, CsA/CyP) are involved in and regulate selective pathways of T cell stimulation.
Murine tumor cells expressing the gene for the human interferon αβ receptor elicit antibodies in syngeneic mice to the active form of the receptor
Authors: Uzé Gilles , Lutfalla Georges , Eid Pierre , Maury Chantal , Bandu Marie‐Thérèse , Gresser Ion , Mogensen Knud 
Published: March 2007

AbstractThe cellular receptor for the human α and β interferons (IFN) was expressed, by gene transfer, in a murine hepatoma‐derived cell line, BTG 9A. Injected subcutaneously into the syngeneic mouse (C57BL/6), the parental and the transfected cells grew and formed tumors which later regressed. More than half the mice bearing tumors derived from cells expressing the receptor, developed IgG antibodies capable of blocking the activity, on human cells, of human recombinant IFN‐αB, ‐αA, ‐αD and of natural human IFN‐β, but not of recombinant IFN‐γ. Cross‐reactivity of human IFN‐α on murine and bovine cells was unaffected by these antibodies. The binding of human IFN‐α to solubilized receptors from human lymphoid cell lines was also blocked and complexes of radiolabeled recombinant IFN‐αA or IFN‐αB, chemically cross‐linked to their human receptor could be immunoprecipitated by the antisera. IFN αβ receptor protein, purified by electrophoresis in sodium dodecylsulfate, was not recognized. We conclude that the antibodies are directed against the forms of the IFN αβ receptor actually expressed on the membrane.
Development of lymphocytes in interleukin 7‐transgenic mice
Authors: Samaridis Jacqueline , Casorati Giulia , Traunecker André , Iglesias Antonio , Gutierrez José C. , Müller Urs , Palacios Ronald 
Published: March 2007

AbstractWe have developed and established mouse transgenic lines in which the mouse interleukin 7 gene was targeted for expression in the lymphoid cell compartment. Northern blot analysis indicate that the transgene is expressed in bone marrow (BM), spleen and thymus, but not in kidney, liver, brain or heart. Both the frequency and absolute numbers of B cell precursors and mature B lymphocytes are increased in the BM and spleen of the transgenic mice. Although there is no expansion of the pro‐T lymphocyte population in the BM, the number of all major subsets of thymocytes and peripheral T lymphocytes is increased in the majority of the transgenic mice analyzed. The B and T cell lymphocytes in the transgenic mice are functionally competent. In contrast, the number of granulocytes and macrophages in the BM of transgenic mice is similar to that in control non‐transgenic littermates. Our results indicate that interleukin 7 plays an important role in vivo in the development of B and T lymphocytes.