bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clonal composition of myelin basic protein‐reactive encephalitogenic T cell populations is influenced both by the structure of relevant antigens and the nature of antigen‐presenting cells
Authors: Sun Deming , Hu Xian‐Zhen , Coleclough Christopher 
Published: March 2007

AbstractStudies of experimental autoimmune encephalomyelitis (EAE) in rodents have revealed that encephalitogenic T cell lines reactive with myelin basic protein (BP) are frequently dominated by clones expressing a restricted T cell receptor repertoire. Using the rat EAE model, we have begun to examine the basis for clonal dominance within BP‐reactive T cell lines. We find that variations introduced into the standard protocol of periodic antigen stimulation produce marked shifts in the representation of different clones within encephalitogenic T cell populations. For example, altering the source of antigen‐presenting cells (APC), while holding antigen (BP) constant, and substituting BP from guinea pig (GPBP) for that of the rat antigen (RBP) with constant APC, both cause shifts in the composition of the dominant clones within BP‐reactive T cell lines. Our results suggest that: (i) adherence to an invariant protocol of antigen challenge may lead to an underestimation of the diversity of BP‐reactive encephalitogenic T cell populations; and (ii) the minor structural differences between GPBP and RBP not only cause the weak immunogenicity of RBP but also result in the alteration of different T cell subsets. These observations indicate that apparent restrictions upon the repertoire of autoimmune T cells should be interpreted with caution when such cells are elicited by immunization with foreign antigens.
Distinct splicing of CD45 mRNA in activated rat γδ cytotoxic T lymphocytes
Authors: Hansson Johan , Dohlsten Mikael , Sjögren Hans‐Olov , Hedlund Gunnar 
Published: March 2007

AbstractPrevious studies have demonstrated tumor‐ and allo‐specific cytotoxic γδ T lymphocytes in rats. In this report we define the surface phenotype of these T cell receptor (TCR)γδ+ T cells and demonstrate distinct CD45 mRNA splicing in activated γδ cytotoxic T lymphocytes (CTL). γδ T lymphocytes in the blood and the peritoneal cavity were TCRαβ−‐CD3+CD8α+CD45RC+ but expressed variable levels of LFA‐1 molecules. Normal peritoneal γδ T lymphocytes, peritoneal γδ T cells from rats injected with the bacterial superantigen staphylococcal enterotoxin A (SEA) as well as γδ T lymphocytes in peripheral blood were all LFA‐1low, Peritoneal γδ T cells from tumor‐, and allo‐sensitized rats were either LFA‐1low or LFA‐1high and specific cytotoxicity was highly enriched in the LFA‐1high subset. No cytolytic activity against SEA‐presenting cells was recorded in γδ T cells from SEA‐injected rats. Different isoforms of CD45 in T cells are generated by alternative mRNA splicing of exons 4, 5, 6 (or A, B and C, respectively) and the recently described alternate exon 7. CD45 splicing in sorted γδ T cells was evaluated utilizing reverse transcription polymerase chain reaction. Normal peritoneal γδ T cells expressed exon(578), exon(678), exon(78) and the extensively spliced exon(8) variant. Peritonealγδ T cells from rats sensitized with irradiated syngeneic tumor cells, allogeneic cells or bacterial superantigen SEA as well as γδ T lymphocytes in peripheral blood contained the full‐length exon(45678), as well as the exon(5678), exon(578), exon(678) and exon(78) splicing products. Notably, the exon(8) variant was also seen in peritoneal γδ T cells of SEA‐sensitized rats. Sorted tumor‐specific LFA‐1high γγ CTL expressed exon(45678), exon(5678), exon(578), exon(678) and exon(78) CD45 splicing products whereas the non‐cytolytic LFA‐1low γδ T cell subset also contained exon(8) variant. In summary, it is concluded that antigen‐specific TCRγδ+ CTL express high levels of LFA‐1 and that the splicing machinery in these cytolytic cells favors expression of the exon(45678) and exon(5678) CD45 splicing products whereas the exon(8) variant is lost. TCRαβ+ CTL express high levels of LFA‐1 but are devoid of the full‐length exon(45678) splicing product. The different CD45 splicing patterns found in αβ CTL and γδ CTL indicate different molecular requirements in respect to CD45 during activation and differentiation of these T lymphocyte subsets.
Epstein‐Barr virus isolates with the major HLA B35.01‐restricted cytotoxic T lymphocyte epitope are prevalent in a highly B35.01‐positive African population
Authors: Lee Stefan P. , Morgan Suzanne , Skinner Julia , Thomas Wendy A. , Jones Sarah Rowland , Sutton Julian , Khanna Rajiv , Whittle Hilton C. , Rickinson Alan B. 
Published: March 2007

AbstractAn influence of cytotoxic T lymphocyte (CTL) response over Epstein‐Barr virus (EBV) evolution was first suggested by the finding that virus isolates from highly HLA‐A11‐positive Oriental populations were specifically mutated in two immunodominant A11‐restricted CTL epitopes. Here we turn to a second HLA allele, B35.01 and show that B35.01‐restricted CTL responses in Caucasian donors reproducibly map to a single peptide epitope, YPLHEQHGM, representing residues 458–466 of the type 1 EBV nuclear antigen 3 A protein (B95.8 strain). In this case, however, most EBV isolates from a highly B35.01‐positive population (in The Gambia) either retained the CTL epitope sequence or carried a mutation (P → S at position 2) which conserved antigenicity; changes leading to reduced antigenicity (Y → N at position 1) were found in only a minority of cases. Furthermore, CTL recognizing the YPLHEQHGM epitope could be reactivated from the blood of some B35.01‐positive Gambian donors by in vitro stimulation with the synthetic peptide, indicating that epitope‐specific immunity does exist in this population. Possible differences between the A11‐based and B35.01‐based studies are discussed.
Human eosinophils express a receptor for secretory component. Role in secretory IgA‐dependent activation
Authors: Lamkhioued Bouchaib , Gounni Abdelillah Soussi , Gruart Valérie , Pierce Annick , Capron André , Capron Monique 
Published: March 2007

AbstractThe existence of a functional receptor for secretory component (SC) on the eosinophil membrane might explain the preferential degranulation induced by secretory IgA (sIgA) when compared to serum IgA. Indeed, flow cytometry analysis revealed that purified human SC could bind to a subpopulation (4–59%) of blood eosinophils purified from 19 patients with eosinophilia. Binding of radiolabeled human SC could be competitively inhibited using unlabeled SC or secretory IgA but not with serum IgA or IgG. Immunoprecipitation and immunosorbent chromatography using human SC revealed the presence of a major component at 15 kDa in eosinophil extracts as well as in culture supernatants but not in neutrophils. The 15‐kDa protein eluted from the human SC immunosorbent was able to bind to SC or to sIgA but not to serum IgA. Eosinophils preincubated with human SC or sIgA released eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) after addition of anti‐SC or anti‐IgA monoclonal antibody as respective cross‐linking reagents. These results indicated that binding of free or complexed SC to human eosinophils could induce eosinophil degranulation. Furthermore, the dose‐dependent inhibition by SC of mediator release induced by sIgA but not by serum IgA, suggested that the receptor for SC could be involved in the preferential degranulation mediated by sIgA. These results indicate a novel pathway of eosinophil activation and its potential involvement in mucosal immunity, particularly in inflammatory diseases associated with infiltration of eosinophils and the enhanced production of sIgA.
Involvement of the interleukin‐2 receptor γ subunit in interleukin‐4‐dependent activation of mouse hematopoietic cells and splenic B cells
Authors: Watanabe Sumiko , Kondo Motonari , Takatsu Kiyoshi , Sugamura Kazuo , Arai Ken‐Ichi 
Published: March 2007

AbstractInterleukin‐4 (IL‐4) has various activities on B cells and on hematopoietic cells. We previously reported that TUGm2, a monoclonal antibody to the γ subunit of the IL‐2 receptor (IL‐2Rγ), inhibited IL‐4‐dependent proliferation of CTLL2, a cytotoxic T cell line. We proposed that IL‐2Rγ is required for the functional IL‐4 receptor (IL‐4R) in T cells. In the present work, we further examined whether or not IL‐2Rγ is involved in IL‐4R function in mouse myeloid cell lines and splenic B cells. TUGm2 suppressed the IL‐4‐induced proliferation of BA/F3 or IC2 cells, as well as of purified splenic B cells. TUGm2 partially suppressed proliferation of B cells induced by the combination of IL‐4 and anti‐immunoglobulin M (IgM) antibody. In contrast, TUGm2 had no effect on proliferation of B cells induced by anti‐IgM antibody alone or lipopolysaccharide (LPS). TUGm2 also inhibited IgE production induced by IL‐4 of LPS‐stimulated B cells. The induction of major histocompatibility complex class II molecules or CD23 by IL‐4 was virtually unaffected by TUGm2 antibody. These results indicate that IL‐2Rγ is differentially involved in various IL‐4‐dependent reactions.
T helper subset involvement in two high antibody responder lines of mice (Biozzi mice): HI (susceptible) and HII (resistant) to collagen‐induced arthritis
Authors: De Franco Marcelo , Gille‐Perramant Marie‐Françoise , Mevel Jean‐Claude , Couderc Jacques 
Published: March 2007

AbstractCD4+ T helper cells play a critical role in the chronicity of collagen‐induced arthritis (CIA) in mice. The present results focus on the involvement of Th1 and Th2 subsets at the initial stage of the experimental disease in two lines of mice selected for high antibody production: HI that is susceptible, and HII that is resistant to CIA. Both lines are known to be H‐2q, display an identical full set of V‐β genes, and mount similar antibody responses to both heterologous and autologous CII. The kinetic analysis of local T cell and anti‐bovine CII antibody responses was followed by Elispot assays, the production of interferon‐γ (IFN‐γ) and IgG2a being considered indicative of a Th1 profile, and interleukin‐5 (IL‐5) as well as IgG1‐IgE, of a Th2 profile. The number of IL‐5 Elispots is constantly higher in susceptible than in resistant mice. The IFN‐γ production is rather low in HI compared to HII, and besides, preferential help is observed for the Th2‐dependent IgG1‐IgE isotype‐producing B cells in HI, while a switch‐over toward IgG2a anti‐CII isotype is found in HII. These results suggest that a Th1 preeminence at the onset of the anti‐CII response is decisive in the resistance to CIA.
Reciprocal expression of co‐stimulatory molecules, B7‐1 and B7‐2, on murine T cells following activation
Authors: Das Mercy R. Prabhu , Zamvil Scott S. , Borriello Frank , Weiner Howard L. , Sharpe Arlene H. , Kuchroo Vijay K. 
Published: March 2007

AbstractThe co‐stimulatory B7 molecules (B7‐1 and B7‐2) are expressed on professional antigen‐presenting cells in mice. In this study, we demonstrate that B7‐1 (CD80) and B7‐2 (CD86) are also expressed on murine T cells in the absence of major histocompatibility complex class II molecules. The temporal expression of these two molecules on T cells varies with the state of activation where resting T cells express B7‐2 but show little or no expression of B7‐1. Following activation, B7‐2 expression is down‐regulated and there is a concomitant increase in the expression of B7‐1 on the cell surface which peaks at about 72 h. Thus these two co‐stimulatory molecules are reciprocally expressed on the T cell surface. This pattern of expression of B7‐1 and B7‐2 on T cells suggests that these two molecules may have different roles in the generation and regulation of immune responses.
Spleen cells from antigen‐minimized mice are superior to spleen cells from germ‐free and conventional mice in the stimulation of primary in vitro proliferative responses to nominal antigens
Authors: Hooper D. Craig , Molowitz Eric H. , Bos Nico A. , Ploplis Victoria A. , Cebra John J. 
Published: March 2007

AbstractT lymphocytes from mice reared under conditions of differential exposure to food, environmental and microbial antigens were compared for phenotypic shifts that may be associated with prior exposure to antigens as well as functional variations in the ability to respond to antigens de novo. While the intra‐epithelial CD8 T cell compartment was found to differ significantly in the type of T cell receptor predominantly expressed, CD4 T cells from various lymphoid organs of conventionally reared specific pathogen‐free (CL‐SPF) mice showed only subtle phenotypic differences from cells obtained from antigen‐minimized germ‐free (AF) and germ‐free (GF) mice. Cells derived from mice exposed to a reduced antigen load exhibited primary in vitro proliferative responses to antigens such as dinitrophenyl‐keyhole limpet hemocyanin which were significantly enhanced when compared with similar responses of cells from conventional mice. In cell mixing experiments, differences in the reactivity of T cells from the spleens of AF, GF and CL‐SPF mice were dependent on the source of the spleen cells employed as antigen‐presenting cells (APC). Experiments in which the T cell population was held constant revealed that, as APC, spleen cells from AF mice were most often superior to spleen cells from GF mice which were in turn considerably better than a similar population from SPF mice. We conclude that the enhanced primary reactivity of spleen cells from AF mice to nominal antigen in vitro is likely to be the result of a difference in the function and/or regulatory activities of the cell population employed as APC in this investigation.
Insertion of a short human immunodeficiency virus (HIV)‐2 gp36 sequence into an HIV‐1 p24 recombinant protein results in a polypeptide with potent and TCRBV‐restricted T cell triggering activity
Authors: Imberti Luisa , Sottini Alessandra , Roldan Eugenia Quirós , Albertini Alberto , Mattioli Sonia , Prati Enrica , Primi Daniele 
Published: March 2007

AbstractIn the present work we investigate whether artificial alterations of the structure of an inactive retrovirus‐encoded protein could transform it in a superantigen. As a model system we used a recombinant human immunodeficiency virus (HIV)‐1 p24 protein and two of its variants in which a short peptide corresponding to sequences of gp41 of HIV‐1 (HIV‐1 p24*) or gp36 of HIV‐2 (HIV‐1‐2 p24*) has been inserted nearby the carboxy‐terminal end of HIV‐1 p24. As expected both HIV‐1 p24 and HIV‐1 p24* were inactive, while HIV‐1‐2 p24* was a potent inducer of human, but not murine, T cell proliferation. The possibility that the observed activity was due to contaminants was ruled out since the proliferative response could be specifically inhibited by a monoclonal anti‐p24 antibody and by a peptide encompassing the area of HIV‐1 p24/HIV‐2 gp36 junction. Furthermore, the data exclude the possibility that the gp36 insertion is per se responsible for the observed proliferative activity.The analysis of the functional, phenotypic and molecular properties of the responding cells demonstrated that the response was class II dependent and that the activated cells were predominantly CD4+CD8− expressing a strongly biased repertoire of TCRBV segments. Collectively, these data strongly suggest that the HIV‐1‐2 p24* fusion protein shares common functional properties typical of superantigen molecules.Thus, our demonstration that a viral protein can be transformed into a superantigen simply by the insertion of a short peptide at the carboxy‐terminal end has important implications for understanding the mode of action of retrovirus‐encoded superantigens.
Evidence for intact costimulation via CD28 and CD27 molecules in hyporesponsive T cells from human immunodeficiency virus‐infected individuals
Authors: Meyaard Linde , Kuiper Heleen , Otto Sigrid A. , Wolthers Katja C. , van Lier René A. W. , Miedema Frank 
Published: March 2007

AbstractIn the activation of T cells, the primary signal is antigen‐specific and given through T cell receptor (TcR)/CD3 ligation. Furthermore, costimulatory molecules such as CD28 and CD27, provide an essential signal for activation through interaction with their ligands, present on the membrane of antigen‐presenting cells. During asymptomatic human immunodeficiency virus (HIV)‐1 infection, T cell function is progressively lost. Here, we investigated whether in the presence of impaired responses of T cells from HIV‐infected individuals to signal one, costimulation through CD28 and CD27 after interaction with their natural ligands CD80 and CD70 is intact. T cell proliferative responses to signal one in combination with CD80 or CD70 were decreased in a large fraction of asymptomatically HIV‐infected individuals. This was due to impaired responses of signal one but not to impaired responses to costimulation, since CD80 or CD70 did enhance signal one‐mediated proliferative responses to a normal extent. Moreover, in individuals with proliferative responses to signal one that were decreased to 50% of normal T cell responses, costimulation even was increased compared to controls.Our results demonstrate that in HIV‐infected individuals the response to costimulation is relatively preserved compared to responses to the first signal and point to the defect in T cells in HIV infection being primarily in the CD3/TcR‐mediated pathway.
Differential effects of gangliosides on human IgE and IgG4 production
Authors: Kimata Hajime 
Published: March 2007

AbstractThe effects of gangliosides on human IgE and IgG4 production were studied. Of the various gangliosides tested, only GM2 and GM3 inhibited the IgE and IgG4 production induced by interleukin (IL)‐4 plus hydrocortisone (HC), or that induced by IL‐13 plus HC, in human surface IgE‐ and IgG4‐negative (sIgE−, sIgG4−) B cells without affecting the production of IgG1, IgG2, IgG3, IgM, IgA1 or IgA2. In contrast, GM1, GD1a, GD1b, GD3, GT1b and GQ1b were without effects. The GM2‐ and GM3‐mediated inhibition was specific, since each was blocked by a corresponding antibody. Of the various factors tested, IL‐6, IL‐10, and tumor necrosis factor (TNF)‐α enhanced the IgE and IgG4 production induced by IL‐4 plus HC or by IL‐13 plus HC, while IL‐8 and transforming growth factor (TGF)‐β inhibited these responses. However, only TNF‐α counteracted the GM2‐ and GM3‐mediated inhibition of IgE and IgG4 production, while IL‐6, IL‐10, anti‐IL‐8 monoclonal antibody and anti‐TGF‐β antibody failed to do so. Anti‐TNF‐α monoclonal antibody, but not control IgG1, not only inhibited IgE and IgG4 production in the absence of TNF‐α but also blocked the counteraction of inhibition by TNF‐α. In cultures containing IL‐4 plus HC or IL‐13 plus HC. GM2 and GM3 specifically inhibited TNF‐α production without affecting TNF‐α receptors, IL‐6 production or IL‐6 receptors. These results indicate that GM2 and GM3 inhibit IgE and IgG4 production by inhibiting endogenous TNF‐α production.
Activated T cells enhance nitric oxide production by murine splenic macrophages through gp39 and LFA‐1
Authors: Tian Licheng , Noelle Randolph J. , Lawrence David A. 
Published: March 2007

AbstractMacrophages can be stimulated to produce a relatively large amount of nitric oxide, which is an important component in macrophage‐mediated defense mechanisms and regulation of T cell activities. It has been known that T helper (Th) cell activation requires intimate physical interaction between T helper cells and macrophages and that cytokines from activated Th cells regulate macrophage activities including nitric oxide production. The current study indicates that surface molecules on activated Th cells also can synergize with cytokines to substantially enhance nitric oxide production by macrophages through cell‐cell contact. The CD40 ligand (gp39) and LFA‐1 appear to be two major contributors for T cell dependent nitric oxide production.
γδ lineage‐specific transcription of human T cell receptor γ genes by a combination of a non‐lineage‐specific enhancer and silencers
Authors: Lefranc Marie‐Paule , Alexandre Daniel 
Published: March 2007

AbstractThe expression of the T cell receptor (TcR) γ genes is restricted to TcR γδ+ T lymphocytes. Transgenic and somatic cell hybrid experiments had suggested that the expression of a functionally rearranged TcR γ gene was extinguished in TcR αP+ T cells, possibly by putative cis‐acting transcriptional silencers. We have identified such negative cis‐acting sequences in the 3′ non‐coding region of the human TcRγ (TRG) locus, upstream of an enhancer located at 6.5 kb of the TcR Cγ2 gene (TRGC2). These silencers were capable of repressing the transcription from a minimal heterologous promoter in a position‐ and orientation‐independent fashion. When analyzed individually, the silencers and the enhancer were equally active in the TcR αβ+ and TcR γδ+ T cell lines studied. In contrast, the association of the enhancer with either silencer was shown to restrict transcription to the TcR γδ+ T cell lines.
Dendritic cells in Leishmania major‐immune mice harbor persistent parasites and mediate an antigen‐specific T cell immune response
Authors: Moll Heidrun , Flohé Stefanie , Röllinghoff Martin 
Published: March 2007

AbstractUpon infection with Leishmania major, a cause of human cutaneous leishmaniasis, mice of resistant strains are able to control the infection, with lesions resolving spontaneously. A long‐lasting cell‐mediated immunity protects them from reinfection. Nevertheless, small numbers of viable parasites persist in the lymph nodes of these mice. We have recently documented that, in addition to macrophages, epidermal Langerhans cells can ingest L. major. Furthermore, Langerhans cells have the unique ability to transport viable parasites from the infected skin to the draining lymph node for presentation to antigen‐specific T cells and initiation of the cellular immune response. During migration, Langerhans cells develop into dendritic cells. In the present study, we analyzed whether dendritic cells support the persistence of parasites in immune hosts. Immunohistological studies and assays in vitro showed that in the lymph nodes of mice that have recovered from infection with L. major, both macrophages and dendritic cells harbor viable parasites. However, only dendritic cells were able to induce a vigorous T‐cell immune response to L. major in vitro in the absence of exogenous antigen. Tracking experiments conducted in vivo suggested that the infected dendritic cells in the lymph nodes are derived from Langerhans cells that have emigrated from the skin. The data demonstrate that L. major‐infected dendritic cells and macrophages in lymph nodes of immune animals represent long‐term host cells, but only dendritic cells have the ability to present endogenous parasite antigen to T cells. Long‐term infected dendritic cells may thus allow the sustained stimulation of a population of parasite‐specific T cells, protecting the mice from reinfection. Our results favor the hypothesis that the persistence of antigen supports the maintenance of T cell memory and that dendritic cells are critically involved in this process.