bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the p70zap tyrosine protein kinase in T cells by the CD45 phosphotyrosine phosphatase
Authors: Mustelin Tomas , Williams Scott , Tailor Pankaj , Couture Clément , Zenner Georg , Burn Paul , Ashwell Jonathan D. , Altman Amnon 
Published: March 2007

AbstractTwo classes of protein tyrosine kinases (PTK) are utilized by the T cell antigen receptor (TcR)/CD3 complex for initiation of the signaling cascade, the Src‐family PTK p56lck and p59fyn, and the Syk‐family PTK p70zap and p72syk. In addition, the CD45 phosphotyrosine phosphatase (PTPase) is required for the induction of tyrosine phosphorylation by the TcR/CD3, presumably by positively regulating Src‐family PTK. Here we report that CD45 also regulates the Syk‐family PTK p70zap (or ZAP‐70). In CD45‐negative T cells, p70zap was constitutively phosphorylated on tyrosine and co‐immunoprecipitated with the TcR‐ζ chain. In resting wild‐type CD45‐positive cells, p70zap was mainly unphosphorylated, but it was rapidly phosphorylated on tyrosine upon treatment of the cells with anti‐CD3 or PTPase inhibitors. Finally, p70zap co‐distributed with CD45 in intact T cells, and tyrosine phosphorylated p70zap was dephosphorylated by CD45 in vitro. These findings suggest that CD45 plays an important role, direct or indirect, in the regulation of p70zap and its function in TcR/CD3 signaling.
Immunoglobulins from rats that are resistant to adjuvant arthritis suppress the disease in arthritis‐susceptible rats
Authors: Ulmansky Rina , Naparstek Yaakov 
Published: March 2007

AbstractThe therapeutic effect of high doses of polyclonal immunoglobulins has been well established in various B cell‐associated autoimmune diseases. In the present work we have examined the effect of low doses of immunoglobulins in adjuvant arthritis, a T cell‐associated disease in the Lewis rat. Lewis rats were treated with purified rat immunoglobulins as well as their Fc and F(ab′)2 fragments and their protective effect on adjuvant arthritis was evaluated. We found that early as well as late treatment with low doses of rat immunoglobulins induced refractoriness to disease induction. The effect was found to be carried out by the F(ab′)2 part of the immunoglobulins and could be adsorbed by affinity purification on Mycobacterium tuberculosis. The protective antibodies were present in Fisher and BN rats that are resistant to adjuvant arthritis, but not in the arthritis susceptible Lewis and Wistar strains. We suggest that resistance to autoimmune arthritis is associated with the presence of protective immunoglobulins and that their effect is carried out through the antigen recognition part of the molecule.
Transforming growth factor‐β inhibits interleukin‐12‐induced production of interferon‐γ by natural killer cells: A role for transforming growth factor‐β in the regulation of T cell‐independent resistance to Toxoplasma gondii
Authors: Hunter Christopher A. , Bermudez Luiz , Beernink Hans , Waegell Wendy , Remington Jack S. 
Published: March 2007

AbstractSevere‐combined immune deficient (SCID) mice have been found to resist infection with the intracellular protozoan parasite Toxoplasma gondii via interleukin (IL)‐12 stimulation of interferon (IFN)‐γ production by natural killer (NK) cells. Previously, we demonstrated the presence of increased levels of transcripts for transforming growth factor‐beta (TGF‐β) in the brains and lungs of SCID mice infected with T. gondii, leading us to investigate the role of TGF‐β in the mechanism of resistance to T. gondii in these mice. Stimulation of splenocytes from SCID mice with heat‐killed T. gondii resulted in production of low levels of IFN‐γ and a two to threefold increase in levels of TGF‐β in the culture supernatants. Production of IFN‐γ in these cultures was increased three to fourfold by addition of anti‐TGF‐β antibody. Stimulation of splenocytes from SCID mice with IL‐12 in combination with either TNF‐α or IL‐1β resulted in production of high levels of IFN‐γ. Addition of TGF‐β to these cultures inhibited production of IFN‐γ in a dose‐dependent manner. Immunohistochemical studies revealed increased levels of TGF‐β protein in the spleens of SCID mice 5 days after oral infection with the ME49 strain of T gondii, and brains of SCID mice at 18 days post‐infection. However, no difference was detected in the levels of TGF‐β transcripts in the spleens of uninfected mice or mice infected for 5 days. To test whether TGF‐β could antagonize IL‐12 mediated resistance to T. gondii in vivo, we administered TGF‐β to SCID mice infected with T. gondii. This treatment resulted in earlier mortality of infected mice and significantly reduced the ability of exogenous IL‐12 to delay time‐to‐death. Administration of anti‐TGF‐β to SCID mice, beginning 24 h prior to infection and every 2 days thereafter, delayed significantly time‐to‐death. Together, our data demonstrate that TGF‐β antagonizes the ability of IL‐12 to stimulate production of IFN‐γ by splenocytes from SCID mice, and suggest a role for TGF‐β in regulation of T cell‐independent resistance to T. gondii.
Heterogenous glycosylation of ICAM‐3 and lack of interaction with Mac‐1 and p150,95
Authors: de Fougerolles Antonin R. , Diamond Michael S. , Springer Timothy A. 
Published: March 2007

AbstractIntercellular adhesion molecule (ICAM)‐1, ICAM‐2, and ICAM‐3 have been identified as counter‐receptors for the leukocyte integrin lymphocyte function‐associated antigen 1 (LFA‐1). The other leukocyte integrins, Mac‐1 and p150,95, also interact with ICAM‐1. ICAM‐1 and ICAM‐3 are highly homologous, and an undefined ligand for Mac‐1 is presnt on neutrophils where ICAM‐3 is well expressed. In addition, glycosylation has been shown to affect the interaction of ICAM‐1 with Mac‐1. We therefore sought to characterize ICAM‐3 heterogeneity and determine whether ICAM‐3 was a ligand for either Mac‐1 or p150,95. Despite extensive differences in N‐linked glycosylation, ICAM‐3 purified from lymphoid cells and from neutrophils supports adhesion of LFA‐1‐bearing cells equally well; however, neither supports adhesion of Mac‐1 or p150,95‐expressing chinese hamster ovary cell transfectants. Similarly, purified Mac‐1 does not support adhesion of ICAM‐2 or ICAM‐3‐expressing L cell transfectants. ICAM‐3 on neutrophils does not participate in Mac‐1‐dependent homotypic aggregation. Thus, ICAM‐3 is not a counter‐receptor for either Mac‐1 or p150,95.
Cytokine‐dependent regulation of growth and maturation in murine epidermal dendritic cell lines
Authors: Xu Shan , Ariizumi Kiyoshi , Edelbaum Dale , Bergstresser Paul R. , Takashima Akira 
Published: March 2007

AbstractWe have recently established dendritic cell (DC) lines (XS series) from the epidermis of newborn mice by repeated feeding with granulocyte/macrophage‐colony‐stimulating factor (GM‐CSF) and culture supernatants from skin‐derived stromal cell lines (NS series). XS lines resemble resident Langerhans cell (LC), which are immature DC that reside in epidermis, by their surface phenotype and antigen‐presenting profile. XS lines further resemble resident LC in that they express mRNA for interleukin‐1β and macrophage inflammatory protein (MIP)‐1α, and by the absence of mRNA for IL‐6. Their growth is promoted by GM‐CSF, colony‐stimulating factor‐1 (CSF‐1), or NS culture supernatant, and inhibited by interferon‐γ or tumor necrosis factor‐α. The expression by the XS lines of la molecules is up‐regulated by GM‐CSF, and down‐regulated by NS supernatant. These results suggest the existence of negative regulatory mechanisms in which the growth and/or maturation of DC is suppressed by selected cytokines.
Rolling of lymphocytes and neutrophils on peripheral node addressin and subsequent arrest on ICAM‐1 in shear flow
Authors: Lawrence Michael B. , Berg Ellen L. , Butcher Eugene C. , Springer Timothy A. 
Published: March 2007

AbstractWe studied leukocyte interactions in shear flow with peripheral lymph node addressin (PNAd), a mixture of glycoproteins expressed on high endothelial venules (HEV) that is required for lymphocyte homing and has been shown to contain a ligand for L‐selectin. T lymphocytes and neutrophils tether and roll on plastic‐immobilized PNAd and E‐selectin at 1.8 dyn/cm2 wall shear stress, but fail to interact with immobilized ICAM‐1, a ligand for LFA‐1 and Mac‐1, at the same flow rate. Cells roll faster on PNAd than on P‐selectin or E‐selectin. L‐selectin mAb inhibit T lymphocyte and neutrophil tethering to PNAd, but do not inhibit T lymphocyte tethering to purified E‐selectin. If allowed to interact with ICAM‐1 under static conditions, phorbol ester‐treated T lymphocytes, but not resting T lymphocytes, are able to form stationary adhesions that withstand the detachment force generated by 36 dyn/cm2 wall shear stress. In contrast, a wall shear stress of 7.3 dyn/cm2 detaches 50% of resting T lymphocytes bound to PNAd. Incubating T lymphocytes on PNAd and ICAM‐1 does not result in adhesion strengthening, suggesting that adhesion through PNAd by L‐selectin does not stimulate lymphocyte LFA‐1 avidity for ICAM‐1. Chemoattractant stimulation of neutrophils or phorbol ester stimulation of lymphoblasts rolling on co‐immobilized PNAd and ICAM‐1 results in rapid arrest and firm sticking, extending the model of sequential selectin‐mediated rolling and subsequent integrin‐mediated firm arrest to lymphocytes and ligands expressed on HEV.
Diacylglycerol lipase activation and 5‐lipoxygenase activation and translocation following TCR/CD3 triggering in T cells
Authors: Cifone Maria Grazia , Cironi Luisa , Santoni Angela , Testi Roberto 
Published: March 2007

AbstractArachidonic acid (AA) release was observed following T cell receptor (TCR)/CD3 complex cross‐linking in different tumor T cell lines as well as on purified peripheral T cells in vivo. Direct measurement of enzymatic activity in vitro of TCR/CD3‐stimulated Jurkat cell extracts on labeled vesicle substrates showed that TCR/CD3 cross‐linking resulted in AA release from sn‐1,2‐diacylglycerol (DAG) vesicles, as detected by TLC analysis, suggesting that DAG lipase was activated following TCR/CD3 stimulation and DAG generation. On the contrary, no phospholipase A2 activation was observed in response to TCR/CD3 stimulation, since no lyso‐phospholipids were generated in vitro from either phosphatidylcholine or phosphatidylinositol‐3,4‐bisphosphate, or from phosphatidic acid vesicles. Moreover, the 1‐DAG lipase inhibitor RHC80267 completely blocked TCR/CD3‐dependent AA release in vitro and in vivo, without effect upon TCR/CD3‐dependent inositol‐1,4,5‐trisphosphate (IP3) generation. Importantly, evidence for further metabolism of released AA was obtained, since synthesis and release of cysteinyl leukotrienes (CLT), but not of leukotriene B4 or cyclooxygenase products, could be detected by radioimmunoassay in different T cell lines and peripheral blood T cells following TCR/CD3 cross‐linking. Moreover, HPLC analysis revealed an accumulation of leukotriene E4 in TCR/CD3 stimulated Jurkat cells. This was associated with translocation of 5‐lipoxygenase from the cytosol to the cell membranes. Finally, TCR/CD3‐mediated CLT production was blocked by MK886, a specific inhibitor of 5‐LO translocation and activation.Our data help define a further level in the fate of second messengers generated after TCR/CD3 triggering and suggest that additional mediators can play a role in the context of T cell activation.
Follicular dendritic cells and B cell chemotaxis
Authors: Burton Gregory F. , Kupp Leo I. , McNalley Erin C. , Tew John G. 
Published: March 2007

AbstractB cells isolated from germinal centers (GC) of immune mice 2–5 days after antigen (Ag) challenge migrate in response to chemotactic signals, whereas GC B cells isolated at other times and resting B cells do not. Since B cells are in direct contact with follicular dendritic cells (FDC) in GC we reasoned that FDC might play a role in enabling B cells to become chemotactically active. Resting B cells were co‐cultured with FDC either with or without anti‐μ‐dextran (anti‐μ‐dex) as an Ag surrogate and/or recombinant interleukin (rIL)‐4 as a T cell surrogate. After 3 days, the B cells were isolated and their migration to chemotactic factors contained in zymosan‐activated serum assessed in microchemotaxis chambers. B cells incubated alone or with anti‐μ‐dex or rIL‐4 showed minimal migration, which could be increased if both anti‐μ‐dex and rIL‐4 were present. However, maximal migration was obtained when B cells were cultured with FDC, and this was not increased by addition of anti‐μ‐dex and/or rIL‐4, indicating that the FDC signal was a primary signal and did not require pre‐activation of the B cells. Checkerboard analysis using variation in concentration and location of the chemoattractant in chemotaxis chambers indicated that both chemotaxis and chemokinesis occurred. B cell migration began within 6 h of culture, peaked by 48 h and decreased thereafter. Removal of FDC or interference with FDC‐B cell contact ablated or significantly decreased induction of B cell migration. Furthermore, induction did not require functional T cells. These data indicate that FDC can induce resting B cells to become responsive to chemotactic signals.
Activation of virus‐specific major histocompatibility complex class II‐restricted CD8+ cytotoxic T cells in CD4‐deficient mice
Authors: Heemskerk Mirjam H. M. , Schilham Marco W. , Schoemaker Henriette M. , Spierenburg Gerrit , Spaan Willy J. M. , Boog Claire J. P. 
Published: March 2007

AbstractAcute enteritic or respiratory disease is a consequence of coronavirus infection in man and rodents. Mouse hepatitis virus, stain A59 (MHV‐A59) causes acute hepatitis in mice and rats and induces a response of major histocompatibility complex (MHC) class II‐restricted CD4+ cytotoxic T cells, protecting mice against acute infection. In the present study we show that MHV‐A59 infection of mice that lack a functional CD4 gene activates effector cells of the CD8+ phenotype. These cytotoxic T cells lyse virus‐infected target cells in a MHC class II‐restricted fashion. The results indicate that CD8+ T cells have the potential to utilize MHC class II as restriction element, illustrating that the immune system can effectively deal with evading microorganisms, such as viruses which down‐regulate MHC class I.
Glycosylphosphatidylinositol‐linked Db does not induce an influenza‐specific cytotoxic T lymphocyte response or recycle membrane‐bound peptides
Authors: Motal Ussama M. Abdel , Sentman Charles L. , Zhou Xianzheng , Robinson Peter J. , Dahmén Jan , Jondal Mikael 
Published: March 2007

AbstractMajor histocompatibility complex (MHC) class I molecules, as well as MHC class I‐bound peptides, are known to recycle between the cell surface and an undefined, endosomal‐like compartment. Little is known about the functional significance of this process. We have explored this using two different forms of the H‐2Db molecule expressed in transgenic mice, either transmembranous (Db‐tm) or with a glycophosphatidylinositol (GPI)‐lipid anchor (Db‐GPI). The recycling capacity of peptides bound to Db‐tm and Db‐GPI was investigated using glycosylated Db‐binding glycopeptides, which were detected by flow cytometry. Only the tm form of Db was found to readily internalize and recycle glycopeptides to the cell surface. When transgenic mice were immunized with influenza A virus (PR8) strain and tested for cytotoxic T lymphocyte (CTL) responses against an immunedominant nucleoprotein epitope (366–374, ASNENMETM), onyl Db‐tm mice were found to generate specific CTL responses. The results support the idea that membrane recycling of MHC class I‐bound peptides on antigen‐presenting cells may be important for the generation of certain CTL responses.
Expression of heat‐stable antigen on tumor cells provides co‐stimulation for tumor‐specific T cell proliferation and cytotoxicity in mice
Authors: Wang Yi‐Chong , Zhu Lihua , McHugh Rebecca , Sell Kenneth W. , Selvaraj Periasamy 
Published: March 2007

AbstractHeat‐stable antigen (HSA/J11d/possibly homologous to CD24), a cell adhesion molecule capable of providing a co‐stimulatory signal for T cell proliferation, is expressed on B cells, activated T cells, monocytes, granulocytes, Langerhans cells and thymocytes. Recent studies have demonstrated that co‐stimulatory signals provided by cell adhesion molecules such as B7‐1 play an essential role in generation of an anti‐tumor immune response. To examine whether the co‐stimulatory signal provided by HSA can induce an anti‐tumor immune response, we have transfected HSA cDNA into the murine melanoma cell line K1735M2, and examined the ability of this transfected cell line to induce tumor‐specific T cell responses. The results demonstrate that spleen cells from mice immunized with HSA‐transfected K1735M2 cells showed enhanced T cell proliferation in a mixed lymphocyte tumor reaction (MLTR) assay and also demonstrated a significant anti‐tumor cytotoxicity to the parent tumor cell (K1735M2). This anti‐tumor cytolytic activity could be abrogated by pretreatment of effector cells with anti‐mouse CD8 monoclonal antibody and complement. Under similar conditions, spleen cells from C3H mice immunized with vector‐transfected K1735M2 cells neither actively proliferate in an MLTR assay, nor did they exert significant cytolytic activity against the respective tumor cells. In summary, our study demonstrated that HSA can provide a co‐stimulatory signal for the T cell immune response against tumor cells in a murine model.
Anergy induction in encephalitogenic T cells by brain microvessel endothelial cells is inhibited by interleukin‐1
Authors: Bourdoulous Sandrine , Béraud Evelyne , Page Christine Le , Zamora Alfredo J. , Ferry Arnaud , Bernard Dominique , Strosberg A. Donny , Couraud Pierre‐Olivier 
Published: March 2007

AbstractExperimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) which can be induced, in susceptible strains like Lewis rats, by transfer of activated myelin basic protein (MBP)‐specific CD4+ T lymphocytes. The role of cerebral endothelium in the onset of EAE, with regard to adhesion, activation and infiltration in the CNS of encephalitogenic T lymphocytes, is not fully understood. When pretreated by interferon‐γ, the immortalized Lewis rat brain microvessel endothelial (RBE4) cells expressed major histocompatibility complex class II molecules and stimulated MBP‐specific proliferation and cytolytic activity of the syngeneic encephalitogenic T cell line, designated PAS. However, RBE4‐stimulated PAS lymphocytes subsequently entered an unresponsive state, known as anergy. When inoculated in syngeneic animals, anergic PAS cells, although still cytotoxic, failed to induce EAE, and no cell infiltration was detectable within CNS. The addition of interleukin‐1β (IL‐1β) during MBP presentation by RBE4 cells prevented T cell anergy induction, and maintained T cell encephalitogenicity, although PAS cells stimulated in these conditions caused delayed and attenuated clinical signs of EAE, with only discrete inflammatory lesions in the CNS, compared with EAE induced by PAS cells fully activated by thymic cells. Altogether, our results indicate that MBP presentation by brain microvessel endothelial cells to encephalitogenic T cells induces T cell anergy and loss of pathogenicity. In addition, IL‐1β co‐stimulation of T cells prevents anergy induction in vitro and at least partially maintains encephalitogenicity in vivo.
Interaction of B and T lymphocyte subsets with high endothelial venules in the rat: binding in vitro does not reflect homing in vivo
Authors: Walter Sebastian , Micheel Burkhard , Pabst Reinhard , Westermann Jürgen 
Published: March 2007

AbstractLymphocytes continuously migrate through the body, and their efficient extravasation from the blood via high endothelial venules (HEV) is essential for initiating an appropriate immune response. Most investigations have focused on the lymphocyte/HEV interaction in vitro. However, to what extent such systems reflect the situation in vivo is not known. It is also unclear whether lymphocyte subsets immigrate into the HEV in proportion to their presence in the blood, and whether import capacity is limited by the HEV. When rat mesenteric lymph node lymphocytes were incubated in vitro on cryostat sections, the well‐known preferential binding of B lymphocytes to HEV of Peyer's patches (PP) and T cells to HEV of axillary lymph nodes (axLN) was observed (axLN vs. PP: B lymphocytes 21.2 ± 5.0% vs. 40.6 ± 11.0%, T lymphocytes 84.6 ± 6.3% vs. 56.5 ± 12.9%). However, when labeled mesenteric lymph node lymphocytes were injected and their location within the HEV was analyzed 15 min later, no preferential interaction was seen. After injection of labeled thoracic duct lymphocytes, the percentage of labeled cells among B and T lymphocytes in the blood was significantly different (4.4 ± 0.9% vs. 8.9 ± 3.6%), whereas that in HEV of axLN (19.0 ± 6.4% vs. 16.6 ± 6.0%) and PP (30.6 ± 6.1% vs. 33.9 ± 4.4%) was comparable. Although the number of injected lymphocytes was similar in magnitude to the total blood lymphocyte pool, after injection there was no increase in lymphocyte numbers in the HEV. Thus, the adhesion assay in vitro does not completely reflect immigration into HEV in vivo. In addition, our data suggest that both the availability of lymphocyte subsets in small venules and the immigration rate into HEV are actively regulated in vivo.
Regulation of T cell receptor (TCR)‐β locus allelic exclusion and initiation of TCR‐α locus rearrangement in immature thymocytes by signaling through the CD3 complex
Authors: Levelt Christiann N. , Wang Baoping , Ehrfeld Angelika , Terhorst Cox , Eichmann Klaus 
Published: March 2007

AbstractDuring thymocyte differentiation, the T cell receptor (TCR)‐β genes are rearranged before the TCR‐α genes. Immature CD4−8− double‐negative thymocytes with a productive rearrangement of the TCR‐β locus are selected to continue maturation to the CD4+8+ double‐positive stage, driven by signals through the pre‐TCR. The signals through the pre‐TCR can be synchronized by injection of mice with anti‐CD3ϵ monoclonal antibody. Using this approach, we demonstrated coordinated induction of a triad of responses in immature thymocytes: arrest of V to DJ rearrangement in the TCR‐β locus, transient down‐regulation of rearrangement‐activating gene (RAG)‐1 and RAG‐2 transcripts, and initiation of germ‐line transcription of the TCR‐α locus. These results suggest that the transition from TCR‐β to TCR‐α locus rearrangement is controlled by signal transduction through the pre‐TCR.
Soluble mouse major histocompatibility complex class II molecules produced in Drosophila cells
Authors: Wallny Hans‐Joachim , Sollami Giuseppina , Karjalainen Klaus 
Published: March 2007

AbstractWe have exploited Drosophila melanogaster. Schneider cells and compatible inducible expression vectors to produce large amounts of secreted major histocompatibility complex (MHC) class II molecules (I‐Ed). A simple two‐step purification protocol was developed. In the first step, recombinant molecules were enriched using a monoclonal anti‐class II antibody column followed by a nickel chelate column which further purified and concentrated the recombinant protein to several mg/ml. Characterization of the purified material indicates that the molecules are correctly assembled into αβ heterodimers. Further analysis shows that the recombinant MHC class II molecules are devoid of endogenous peptides and, therefore, homogenous peptide/MHC complexes could be prepared by adding exogenous I‐Ed‐specific peptides at slightly acidic pH. Upon peptide addition, molecules underwent a conformational change into a more compact form revealed by gel filtration analysis. In addition, the peptide/MHC complexes were biologically active. As little as 10 ng of these complexes coated on plastic from a 100 ng/ml solution were sufficient to trigger antigen‐specific T cell hybridomas. These MHC class II molecules, together with various forms of soluble T cell receptor (TcR) proteins, provide valuable tools to analyze the molecular details of TcR/antigen recognition.