bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunization of mice with the N‐terminal (1–272) fragment of simian virus 40 large T antigen (without adjuvants) specifically primes cytotoxic T lymphocytes
Authors: Schirmbeck Reinhold , Zerrahn Jens , Kuhröber Andreas , Deppert Wolfgang , Reimann Jörg 
Published: March 2007

AbstractImmunization of C57BL/6 (B6) mice (H‐2b) with the “large tumor antigen” (T‐Ag) of simian virus 40 (SV40) in its soluble form without adjuvants primed CD8+ cytotoxic T lymphocytes (CTL) in vivo. CD8+ CTL primed in vivo by this non‐structural 708‐amino acid (aa) viral protein, and specifically restimulated in vitro, lysed H‐2b target cells, either transfected with an SV40 T‐Ag‐encoding vector, or transformed by SV40 infection. H‐2b RMA‐S transfectants expressing the complete 708 aa T‐Ag (which fail to transport peptides through the endoplasmic reticulum membranes) were not lysed. CTL were also efficiently primed in vivo by injection of the N‐terminal 272 aa fragment of the T‐Ag. Hence, this fragment contains the structure (s) required for a soluble protein to enter the “endogenous” class I‐restricted antigen processing and presentation pathway for CD8+ CTL activation. In soluble form, the complete T‐Ag or the N‐terminal T‐Ag fragment sensitized in vitro RBL5 cells for lysis by T‐Ag‐specific CTL lines and clones. This in vitro sensitization was blocked by brefeldin A. In contrast, specific recognition of RBL5 cells pulsed in vitro with synthetic, immunogenic nonapetides (derived from N‐terminal T‐Ag epitopes) by CTL lines was insensitive to brefeldin A. Hence, T‐Ag and its 272‐aa N‐terminal fragment can enter the “endogenous” processing pathway and prime CD8+ CTL in vivo and in vitro.
T cell activation by a Trypanosoma brucei brucei‐deriyed lymphocyte triggering factor is dependent on tyrosine protein kinases but not on protein kinase C and A
Authors: Bakhiet Moiz , Mix Eilhard , Kristensson Krister , Wigzell Hans , Olsson Tomas 
Published: March 2007

AbstractTrypanosoma brucei brucei releases a lymphocyte‐triggering factor (TLTF) that activates CD8+ T cells. We here study second messenger mechanisms in this activation, i. e. the effects of protein kinase C (PKC), protein kinase A (PKA) and tyrosine kinases (TPK) inhibitors on TLTF‐induced interferon‐γ (IFN‐γ) secretion and proliferation in lymphoid cell cultures. The effects were compared to those obtained by phytohemagglutinin (PHA) stimulation. Rat spleen mononuclear cells (MNC) and spleen MNC from a mutant mouse strain possessing CD8+ T cells but lacking CD4+ T cells were used as responder cells.Although both the PKC and the PKA inhibitors suppressed PHA‐induced IFN‐γ secretion and proliferation of rat MNC and mouse CD8+CD4− MNC, they had no effect on the same TLTF‐induced responses. The TPK inhibitor genistein, however, strongly suppressed TLTF‐induced activation of both types of responder cells to IFN‐γ secretion and the TLTF‐induced proliferation of mouse CD8+CD4− MNC. The suppressive effects of the drugs could be overcome by ionomycin and tetradecanoylphorbol acetate, which show that the effects were not due to drug nonspecific cellular toxicity of the drugs. We conclude that TLTF activates CD8+ T cells through pathways other than the PKC‐ or PKA‐dependent signal transduction, and that TPK may be involved in the triggering.
Lysis of infected cells in vivo by antiviral cytolytic T cells demonstrated by release of cell internal viral proteins
Authors: Kyburz Diego , Speiser Daniel E. , Battegay Manuel , Hengartner Hans , Zinkernagel Rolf M. 
Published: March 2007

AbstractImmunocompetent adult mice infected with lymphocytic choriomeningitis virus (LCMV) generate a strong antiviral cytotoxic T cell response that clears virus from all organs. Although there is good evidence that immune cytotoxic T lymphocytes (CTL) kill target cells in vitro, in vivo it is debated whether antiviral activity of CD8+ T cells is mediated via direct target cell lysis or via soluble mediators.To demonstrate CD8+ T cell‐mediated destruction of infected cells in vivo a specific cell‐internal releasable marker was used as label, i.e. the nucleoprotein (NP) of LCMV. Since LCMV is non‐cytopathic the viral NP will only be released in substantial amounts because of destruction of infected host cells by immune CTL. It is shown here that the amount of NP released from infected and 51Cr‐labeled target cells in vitro correlated well with the amount of radioactivity released. Viral NP released in vivo by CTL is bound and masked by the anti‐NP antibodies that are produced very early and efficiently. However, NP could readily be detected in sera of LCMV‐infected CD8+ competent mice that could not generate antibodies specific for the NP because they were treated with a depleting anti‐CD4 antibody. NP was also detected in the cerebrospinal fluid of mice suffering from CD8+ T cell‐mediated lymphocytic choriomeningitis after intracerebral infection. NP titers in sera of anti‐CD4‐treated LCMV‐infected mice exhibited a peak around day 7–8 when CTL activity was highest. When mice were CD8 T cell‐depleted with anti‐CD8 monoclonal antibody or in LCMV‐carrier mice, no NP was detected in the serum. Highly activated LCMV‐specific CTL adoptively transfused to LCMV‐infected irradiated recipient mice also caused a time‐dependent release of NP into serum. This confirms that the CD8+ population is responsible for the release of NP from infected host cells. These results represent an in vivo correlate of CTL‐mediated cytolysis and evidence that antiviral cytotoxic T cells are cytolytic in vivo. They also suggest that antibody responses to internal antigens of non‐cytopathic viruses may signal CD8+ Tcell‐mediated destruction of infected host cells.
The extended hinge region of IgG3 is not required for high phagocytic capacity mediated by Fcγ receptors, but the heavy chains must be disulfide bonded
Authors: Aase Audun , Sandlie Inger , Norderhaug Lars , Brekke Ole Henrik , Michaelsen Terje E. 
Published: March 2007

AbstractFeγ receptor (FcγR) phagocytosis and respiratory burst were induced by chimeric mouse‐human anti‐(4‐hydroxy‐5‐iodo‐3‐nitrophenyl) acetyl IgG3 antibodies with mutations in hinge and/or in CH1 region. IgG3 mutants with different hinge length ranging from 47 to 0 amino acids, an IgG3 molecule with an artificial hinge of just one cysteine residue (HM‐1), and two hybrid IgG3 molecules with IgG4 hinge or IgG4 CH1‐hinge were tested. Using the monocytic cell line U937 as effector cells, the mutated IgG3 molecules were very similar, revealing high activity, while the IgG3/IgG4 hybrids revealed a slightly reduced activity. However, the hingeless (0‐h) mutant was negative, except after interferon‐γ stimulation when it became slightly positive. Interestingly, HM‐1 was as active as the IgG3 mutants. With polymorphonuclear leucocytes (PMN) as effector cells we obtained some day‐to‐day variations, but all the IgG3 mutants were highly active, with the two shortest hinge mutants somewhat less active The IgG3/IgG4 hybrid molecules revealed an intermediate activity, while IgG4 wild‐type and the 0‐h mutant were negative. However, the HM‐1 molecule revealed an activity similar to that of the IgG3 mutants. The phagocytic activity of U937 was inhibited by monomeric IgG, indicating the importance of FcγR III. In contrast, with PMN both blockage of FcγRII and cleavage of FcγRIII were required to significantly reduce the phagocytosis and respiratory burst, thus showing that both receptors contribute to the effect. These results demonstrate that the extended IgG3 hinge region is not necessary for a high phagocytic activity and that the major structural importance of the hinge is to connect the two heavy chains in this region.
Propriocidal apoptosis of mature T lymphocytes occurs at S phase of the cell cycle
Authors: Boehme Stefen A. , Lenardo Michael J. 
Published: March 2007

AbstractWe found that mature nontransformed CD4+ and CD8+ T lymphocytes could be made susceptible to T cell receptor(TcR)‐mediated apoptosis by pretreatment with interleukin‐4 (IL‐4) or interleukin‐2 (IL‐2). The degree of susceptibility to death could be correlated with the level of cell cycling as measured by thymidine incorporation, cell doubling times, or the number of cells incorporating bromodeoxyuridine during S phase. However, using pharmacologic cell cycle blocking agents, we found that progression through the cell cycle was not required for cell death. Rather, we found that cells must be in a certain phase of the cell cycle to be susceptible to TcR‐mediated death. Cells blocked in G1 phase were resistant to T cell receptor‐induced apoptosis, whereas cells blocked in S phase were susceptible. These observations suggest that an important feature of growth lymphokines is their ability to drive T cells into portions of the cell cycle where they are sensitive to antigen receptor‐induced apoptosis. Furthermore, these results provide additional evidence that the T cell growth lymphokines IL‐2 and IL‐4 may participate in the down‐regulation of T cell responses by apoptosis a pathway we have termed “propriocidal regulation”.
Nocardia fractions, NLD and NWSM, induce tumor necrosis factor‐α secretion in human monocytes: Role of protein kinase C
Authors: Mege Jean Louis , Jacob Thiery , Bongrand Pierre , Capo Christian , Myssiakine Evguenine B. , Barot‐Ciorbaru Rita 
Published: March 2007

AbstractNocardia lysozyme digest (NLD) and Nocardia water‐soluble mitogen (NWSM) are two fractions derived from Nocardia opaca. In this report, we demonstrated that both fractions elicited significant secretion of tumor necrosis factor‐α (TNF‐α) in human monocytes. Supernatants from monocytes stimulated with NWSM and low concentrations of NLD displayed a cytotoxic activity against TNF‐α‐sensitive L929 cells, but supernatants from monocytes stimulated with high concentrations of NLD failed to lyse L929 cells. This latter phenomenon might be related to the secretion of an inactive form of TNF‐α or the release of an inhibitor of TNF‐α cytotoxic activity. Since it is well established that protein kinase C (PKC) plays a major role in the signaling of several monocyte activators, we investigated the putative role of PKC in cytokine synthesis induced by NLD and NWSM fractions. TNF‐α secretion in response to both Nocardia fractions was inhibited by sphingosine, staurosporine and calphostin C, known PKC inhibitors, as well as by a PKC depletion procedure. In addition, NLD and NWSM induced a transient increase in [3H] phorbol dibutyrate binding, which assessed the activation of PKC. The data suggest the involvement of PKC in the signaling of NLD and NWSM fractions leading to the synthesis and the secretion of TNF‐α by human monocytes.
Resistance to collagen‐induced arthritis in rats and rhesus monkeys after immunization with attenuated type II collagen
Authors: 't Hart Bert A. , Bakker Nicolaas P. M. , Jonker Margreet , Bontrop Ronald E. 
Published: March 2007

AbstractImmunization of susceptible rodent or primate species with type II collagen (b‐CII) from bovine origin induces type II collagen‐induced arthritis (CIA). The disease is characterized as a systemic polyarthritis associated with humoral and cellular autoimmunity to CII and shares similarity with human arthritic diseases. The objective of this study was to develop a procedure for induction of resistance to CIA in animals, which possess a certain major histocompatibility complex phenotype that makes them prone to develop CIA (susceptible). It is shown that by immunization with an attenuated form of CII, in which arthritogenic epitopes have been destroyed by heat denaturation, disease resistance is induced in a susceptible inbred rat strain (RT‐1U) and in an outbred population of susceptible rhesus monkeys (lacking the Mamu‐A26 allele). In both species the disease resistance is connected with modulation of anti‐CII autoantibodies of the IgM isotype. This protocol may provide a basis for effective and safe methods to induce protection to autoimmune arthritis in those subjects that are genetically prone to develop such a disease.
Analysis of intraepithelial lymphocytes from major histocompatibility complex (MHC)‐deficient mice: No evidence for a role of MHC class II antigens in the positive selection of Vδ4+γδ T cells
Authors: Schleussner Cathrin , Ceredig Rhodri 
Published: March 2007

AbstractThree‐color flow cytometric analysis was carried out with intraepithelial lymphocytes from mice deficient in expression of major histocompatibility complex (MHC) antigens. These experiments were done to address the possible role of MHC class II molecules in the positive selection of Vδ4+ γδ T cells. By analyzing mice deficient MHC class II antigens alone or in combination with MHC class I antigens, no evidence was found for positive selection of Vδ4+ cells among CD8a+ or CD4−CD8− subpopulations of γδ T cell receptor‐positive cells. Because V54+, CD8a+ cells were reported to be positively selected on I‐Ek and hybrid I‐Ek/b molecules, class II‐deficient animals were crossed with I‐Ek transgenic mice and progeny examined for Vδ4 expression. Again, no evidence for positive selection was found. Interestingly, in MHC class I‐deficient animals, the total number of γδ T cells was about twofold higher than in control and MHC class II‐deficient mice and the proportion of V8δ‐expressing cells was correspondingly decreased. Taken together, these results cast doubt on a major role for conventional MHC antigens in shaping the γδ T cell repertoire of intraepithelial lymphocytes.
The T cell receptor associated CD3‐ϵ protein is phosphorylated upon T cell activation in the two tyrosine residues of a conserved signal transduction motif
Authors: Sancho Jaime , Franco Rafael , Chatila Talal , Hall Craig , Terhorst Cox 
Published: March 2007

AbstractSignal transduction through the Tcell receptor for antigen, the TcR/CD3 complex, involves phosphorylation of tyrosine residues in the CD3‐ϵ chain. Since both CD3‐ϵand the ζ, chain contain a tyrosine‐based signaling motif, we examine phosphorylation of CD3‐ϵ in human T cells. Engagement of the TcR/CD3 complex induced tyrosine phosphorylation of CD3‐ϵ in vivo. Induction of CD3‐ϵ phosphorylation followed similar kinetics to that of the ζ, chain phosphorylation. In contrast to ζ, CD3‐ϵ phosphorylation was strictly dependent upon cell surface expression of this member of the TcR/CD3 complex. Chemical and proteolytic cleavage combined with peptide‐specific Western blotting established that CD3‐ϵ phosphorylation occurred in the two tyrosine residues located in the signal transduction motif in the C‐terminal portion of the molecule. Taken together, these data indicated that phosphorylation of CD3‐ϵ by tyrosine protein kinases may serve to couple the TcR/CD3 complex to other effector molecules in the signaling cascade.
Molecular characterization of the early activation antigen CD69: A type II membrane glycoprotein related to a family of natural killer cell activation antigens
Authors: Ziegler Steven F. , Ramsdell Fred , Hjerrild Kathryn A. , Armitage Richard J. , Grabstein Kenneth H. , Hennen Kathryn B. , Farrah Terry , Fanslow William C. , Shevach Ethan M. , Alderson Mark R. 
Published: March 2007

AbstractCD69 is a disulfide‐linked homo‐dimer expressed on the surface of activated T cells, B cells, natural killer cells, neutrophils and platelets. Antibody cross‐linking of CD69 in the presence of phorbol ester results in cellular activation events including proliferation and the induction of specific genes. Using an expression cloning strategy we have isolated cDNA encoding human CD69 from a CD4+ T cell clone. Transfection of the cDNA clone in CV‐1/EBNA cells results in the expression of a covalently linked homodimer. The cDNA insert hybridizes to a 1.7‐kb mRNA in phorbol 12‐myristate 13‐acetate‐ or phytohemoagglutinin‐stimulated human T cells. Using the human clone we have isolated cDNA encoding mouse CD69, which, when expressed in human T cells allowed those cells to respond to anti‐mouse CD69 antibodies by secreting interleukin‐2 and interferon‐γ. Sequence analysis showed that both mouse and human CD69 are type II membrane glycoproteins related to the NKR‐P1 and Ly‐49 families of natural killer cell activation molecules.
Development of γδ T cells in the adult murine thymus
Authors: Zorbas Michelle , Scollay Roland 
Published: March 2007

AbstractThe development of T cells belonging to the γδ lineage is not well understood. We have analyzed the cells in the adult murine thymus which express the γδ TcR on the surface in order to learn more about this process. Our data demonstrate a number of clear subpopulations of γδ expressing cells in the thymus based on the expression of Thy‐1 and HSA (heat‐stable antigen). Only one of these subpopulations, the one expressing both Thy‐1 and HSA, contains dividing cells or has a significant rate of turnover. Together with the fact that emigrant γδ cells are HSA+Thy‐1+, this suggests that this thymic subpopulation is the sole, or major, source of exported cells. However, the turnover of cells from this population is 5 × 104 ‐ 10 × 104 cells per day, while previous estimates of the rate of export of γδ cells are in the order of 104 cells per day. Furthermore the Vγ profile of recent γδ+ emigrants differs from that of the thymic HSA+Thy‐1+ cells. This raises the possibility that only a selected subpopulation of the thymic γδ+HSA+Thy‐l+ population is exported, and that some γδ cells may die in situ in the thymus. The function of the other γδ thymic subpopulations, which are turning over very slowly or not at all, (i.e. the HAS−Thy‐l− and HAS−Thy‐l+ subpopulations) remains unclear.
Restricted expression of transgenic HLA‐DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self‐superantigens and processed DRα‐derived peptide
Authors: Fukui Yoshinori , Yamamoto Ken , Yokoyama Nobuhiko , Iwanaga Tomohisa , Kurashima Chieri , Esaki Yukio , Kimura Akinori , Akashi Takumi , Hirokawa Katsuiku , Sasazuki Takehiko 
Published: March 2007

AbstractWe have established a set of transgenic mouse lines in which the HLA‐DRA gene was expressed in different cell types. In one line (DRα‐24), DRαEβb molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow‐derived antigen‐presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DRα‐30) was found on thymic medullary and cortical epithelial cells but not on bone marrow‐derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DRα‐24 and DRα‐30 was performed. In DRα‐30, T cells expressing TcR Vβ5 and Vβ11 were eliminated to comparable levels to those in DRα‐24, suggesting that expression of the DRαEβb molecules on thymic epithelial cells are sufficient for clonal deletion of the self‐superantigen‐reactive T cells. In addition, CD4+ T cells from DRa‐30 as well as those from DRα‐24 were tolerant to DRα‐derived peptide/I‐Ab complex expressed on spleen cells from DRα‐24 even in the presence of exogenous interleukin‐2. These observations suggest that expression of the DRα chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DRα‐derived peptide bound to I‐Ab molecules, probably via clonal deletion of the self‐reactive T cells.
Interleukin‐9 potentiates the interleukin‐4‐induced immunoglobulin (IgG, IgM and IgE) production by normal human B lymphocytes
Authors: Dugas Bernard , Renauld Jean Christophe , Pène Jerome , Bonnefoy Jean Yves , Peti‐Frère Corinne , Braquet Pierre , Bousquet Jean , Van Snick Jacques , Mencia‐Huerta Jean Michel 
Published: March 2007

AbstractIgE production by normal peripheral blood lymphocytes (PBL) is known to be triggered upon stimulation by interleukin (IL)‐4. In the present study we showed that IL‐9, another T cell‐derived cytokine, markedly potentiated IgE production induced by suboptimal doses of IL‐4, whereas no effect of IL‐9 was observed in the absence of IL‐4. The potentiating effect of IL‐9 appeared to be associated with the increased frequency of IgE‐producing cells, as revealed by a specific ELISA‐spot assay. Under the same experimental conditions, IL‐9 also enhanced the IL‐4‐induced IgG production but did not elicit IgM production. However, IL‐9 did not amplify the IL‐4‐dependent expression of membrane‐bound and soluble low affinity receptor for IgE (CD23). IL‐4‐induced IgE production was also potentiated by IL‐6 but not by tumor necrosis factor‐α and IL‐β The possibility that the activity of IL‐9 was mediated by IL‐6 released from accessory cells was excluded by the observations that monocyte depletion did not abolish the effect of IL‐9 and that IL‐9 was still active on fluorescence assisted cell sorted CD20+ B lymphocytes co‐cultured with irradiated murine EL4 cells. In addition, IL‐9 was shown to potentiate the IL‐4‐induced IgG and IgM production by normal human B lymphocytes preactivated with Staphylococcus aureus Cowan strain. Taken together, these data suggest that IL‐9 plays a regulatory role in the IL‐4‐dependent immunoglobulin production.
The influence of rearranged T cell receptor αβ transgenes on early thymocyte development
Authors: Nikolić‐Žugić Janko , Andjeli Sofija , Teh Hung‐Sia , Jain Nada 
Published: March 2007

AbstractMost murine thymocytes and mature T cells originate from a numerically minor population of CD8−4− (double‐negative, DN) thymocytes. In this study, we investigated the effects of rearranged T cell receptor (TcR) α and β transgenes on early T cell development. We analyzed the precursor potential, the expression of CD25 and TcR at mRNA and/or protein level in DN thymocyte subsets in TcR transgenic (Tg) mice. We report the following observations: (i) despite a large overrepresentation of total DN cells in TcR Tg mice, precursor‐containing CD25+ DN and CD810410 thymocytes are reduced to a third of the nontransgenic control numbers; (ii) like in the normal mice, CD25+ DN and CD810410 can, and TcR+ DN cells cannot generate other thymic subsets; (iii) TcR α mRNA and TcR α/β protein levels are quantitatively increased, but their developmental expression is similar to that in normal mice; and (iv) surface TcR αβ expression becomes detectable as the thymocytes down‐regulate CD25, paralleling the situation in normal mice. Our findings implicate stringent transcriptional control, rather than TcR gene rearrangement, as a decisive regulator of TcR αβ expression in early ontogeny.