bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte chemotactic protein‐3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils
Authors: Xu Luo Ling , McVicar Daniel W. , Ben‐Baruch Adit , Kuhns Douglas B. , Johnston James , Oppenheim Joost J. , Wang Ji Ming 
Published: March 2007

AbstractThe diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high‐affinity binding for 125I‐MCP3 with an estimated Kd of 1–3 nM and about 10000 binding sites/cell. The binding of 125I‐MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)lα (Kd = 5–10 nM), RANTES (Kd = 5–10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1β (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1α, RANTES, MCP1 and MIP1β as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1α and RANTES. However, MIP1α and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross‐desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1α, RANTES and MCP1. The unidirectional competition for MIP1β binding and signaling by MCP3 suggests the existence of an as‐yet unidentified site for MCP3 shared with MIP1β. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor.
Physical association and functional relationship between protein kinase Cζ and the actin cytoskeleton
Authors: Gómez Javier , de Aragón Ana Martínez , Bonay Pedro , Pitton Christina , García Alphonse , Silva Augusto , Fresno Manuel , Alvarez Fernando , Rebollo Angelita 
Published: March 2007

AbstractProtein kinase C (PKC) was initially identified as a serine/threonine protein kinase dependent on calcium and phospholipids and shown to be involved in intracellular signaling pathways. PKC isoforms have been classified into four groups: Ca2+‐dependent conventional PKC α, βI, βII, γ; Ca2+‐independent, novel PKC δ, ϵ, η, θ; atypical PKCζ, λ, ι which are not activated by Ca2+ or diacylglycerol, and the recently discovered PKCμ. We reported that activation of the ζ PKC isoform is an important step in interleukin‐2 (IL‐2)‐mediated proliferation (Gómez, J., Pitton, C., García, A., Martínez, A., Silva, A. and Rebollo, A., Exp. Cell Res. 1995. 218: 105.). ζPKC is also required for mitogenic activation of fibroblasts and for the maturation pathway activated by insulin and Ras. Contradictory results have been reported regarding the subcellular redistribution of ζPKC upon activation. We report here, using confocal microscopy, that IL‐2 induces expression, translocation and association of ζPKC to a structure coincident with the actin cytoskeleton. Furthermore, we show that ζPKC has a role in maintaining the integrity of the actin cytoskeletal structure in IL‐2‐stimulated cells. On the contrary, ζPKC is not involved in the actin cytoskeleton organization when cells are maintained in IL‐4, confirming our previous results showing that IL‐4‐induced signal transduction is PKC independent.
Evidence that productive rearrangements of TCR γ genes influence the commitment of progenitor cells to differentiate into αβ or γδ T cells
Authors: Kang Joonsoo , Baker Jeanne , Raulet David H. 
Published: March 2007

AbstractTwo models have been considered to account for the differentiation of γδ and αβ T cells from a common hematopoietic progenitor cell. In one model, progenitor cells commit to a lineage before T cell receptor (TCR) rearrangement occurs. In the other model, progenitor cells first undergo rearrangement of TCRγ, δ, or both genes, and cells that succeed in generating a functional receptor commit to the γδ lineage, while those that do not proceed to attempt complete β and subsequently α gene rearrangements. A prediction of the latter model is that TCRγ rearrangements present in αβ T cells will be nonproductive. We tested this hypothesis by examining Vγ2‐Jγ1Cγ1 rearrangements, which are commonly found in αβ T cells. The results indicate that Vγ2‐Jγ1Cγ1 rearrangements in purified αβ T cell populations are almost all nonproductive. The low frequency of productive rearrangements of Vγ2 in αβ T cells is apparently not due to a property of the rearrangement machinery, because a transgenic rearrangement substrate, in which the Vγ2 gene harbored a frame‐shift mutation that prevents expression at the protein level, was often rearranged in a productive configuration in αβ T cells. The results suggest that progenitor cells which undergo productive rearrangement of their endogenous Vγ2 gene are selectively excluded from the αβ T cell lineage.
Differential expression of the T cell receptor/CD3 genes and their lymphoid‐specific transcription factor genes in murine T cell x fibroblast and T cell x B cell hybrids
Authors: Yamada Toshiyuki , Hitomi Yoshiaki , Satake Masanobu , Oikawa Tsuneyuki 
Published: March 2007

AbstractWe generated cell hybrids between mouse T cell lymphoma EL4 cells and mouse fibroblast B82 cells (BELIII and BELIV) to examine the expression of T cell receptor (TcR)/CD3 genes and their lymphoid‐specific transcription factor genes, which are normally detected in EL4 cells. In BELIII and BELIV, expression of the TcRα, TcRβ and CD3δ genes was extinguished, whereas expression of the CD3ϵ gene was still detected. Expression of the (lymphoid enhancer binding factor 1) LEF‐1 gene was extinguished and that of the GATA‐3 gene was hardly detected in BELIII and BELIV. Ets‐1 gene expression, observed not only in EL4 cells but also in B82 cells, was considerably reduced in BELIII and BELIV. A much higher level of PEBP2αA gene expression was observed in B82 cells than in EL4 cells and was preserved in BELIII and BELIV. To examine whether reduced expression of these genes is also found in T cell x B cell hybrids, we generated an additional cell hybrid between EL4 cells and mouse plasmacytoma S194 cells (SELIII). Marked differences were observed in the expression of the TcRα, CD3δ, LEF‐1 and PEBP2αA genes in BEL and SEL hybrids. Expression of the TcRα, CD3δ and LEF‐1 genes, which was extinguished in BELIII and BELIV, was detected in SELIII. PEBP2αA gene expression, not detected in S194 cells, was considerably reduced in SELIII. Almost the sum of the chromosomes from the parental cells were retained by, and the presence of every gene was proven, in each cell hybrid. These results suggest that suppression of the expression of lymphoid‐specific transcription factor genes may precede that of the TcR/CD3 genes in the cell hybrids, and that the presence of a different trans‐acting negative regulatory mechanism(s) suppresses the expression of T cell specific genes in fibroblasts and B cells.
Inhibition of resistance to hemopoietic allo‐grafts in granulocyte colony‐stimulating factor transgenic mice
Authors: Kokai Yasuo , Kaneko Hideo , Izuka Kooh , Matsuura Akihiro , Fujimoto Junichiro 
Published: March 2007

AbstractTransplanted allogeneic marrow cells often fail to engraft in a lethally irradiated host. This phenomenon, termed resistance to allogeneic marrow grafts or allo‐resistance, is well documented, although its mechanism is not yet understood. Transplantation of major histocompatibility complex disparate allogeneic marrow cells into mice transgenic for granulocyte colony‐stimulating factor (G‐CSF) showed donor‐derived spleen colonies (CFU‐S) and resulted in stable allogeneic chimerism with excellent survival (100% up to 40 days and 89% up to 120 days). Under the same experimental conditions, all the littermate controls failed to show CFU‐S and died shortly after marrow transplantation. Thus, resistance to allogeneic marrow cells appeared to be severely impaired in this transgenic mouse. The observation that neutralizing antibody against G‐CSF restored allo‐resistance in G‐CSF transgenic mice and that CFU‐S was inducible upon administration of recombinant G‐CSF using a mini‐osmotic pump in non‐transgenic recipients, suggests that an elevated level of this cytokine is important for the inhibition of allo‐resistance. Thus, G‐CSF was found to play a role in allogeneic resistance to marrow grafts and the G‐CSF‐transgenic mice provide a useful model to study the inhibition of the resistance. The inhibition of allo‐resistance may be useful in preparing allogeneic bone marrow chimeras in both experimental and clinical settings.
Interleukin‐10 inhibits cytokine generation from mast cells
Authors: Arock Michel , Zuany‐Amorim Claudia , Singer Monique , Benhamou Marc , Pretolani Marina 
Published: March 2007

AbstractThis report examines the effect of recombinant murine interleukin‐10 (rmIL‐10) on antigen‐induced β‐hexosaminidase, leukotriene (LT)C4 and cytokine release from mouse bone marrow‐derived mast cells (BMMC). BMMC sensitized to hapten‐monoclonal IgE directed against dinitrophenol‐bovine serum albumin (DNP‐BSA) and challenged with 10 ng/ml DNP‐BSA generated β‐hexosaminidase and LTC4‐like material, which was followed by tumor necrosis factor‐α (TNF‐α) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) mRNA expression and protein release. Incubation of BMMC with 1–100 ng/ml rmIL‐10 inhibited cytokine generation, without affecting β‐hexosaminidase and LTC4‐like material release. TNF‐α, but not GM‐CSF mRNA expression, was also diminished in rmIL‐10‐treated BMMC, suggesting that down‐regulation of cytokine production by rmIL‐10 involves different mechanisms. These results identify a novel biological action of IL‐10 as an inhibitor of cytokine production by stimulated mast cells.
Specific expression of surface interferon‐γ on interferon‐γ producing T cells from mouse and man
Authors: Assenmacher Mario , Scheffold Alexander , Schmitz Jürgen , Checa Juan Antonio Segura , Miltenyi Stefan , Radbruch Andreas 
Published: March 2007

AbstractInterferon (IFN)‐γ is a potent immunoregulatory protein secreted by CD4+ and CD8+ T cells and by natural killer cells. Here, we show that IFN‐γ is specifically displayed at a low concentration on the cell surface of those activated T cells from mouse and man which express IFN‐γ. It is transiently expressed on the cell surface with kinetics similar to those of intracellular IFN‐γ expression. Detectable surface IFN‐γ is not expressed by activated T helper (Th) cells producing other cytokines but which do not express IFN‐γ. Thus, surface IFN‐γ is the first available marker for live T lymphocytes expressing IFN‐γ, e.g. Th1 cells.
Blimp‐1 overcomes the block in IgM secretion in lipopolysaccharide / anti‐μ F(ab′)2‐co‐stimulated B lymphocytes
Authors: Schliephake Dorothee E. , Schimpl Anneliese 
Published: March 2007

AbstractA combination of signals transmitted through the antigen receptor, membrane‐bound cell interaction molecules and cytokine receptors induces B cell proliferation and differentiation into immunoglobulin‐secreting or memory cells. It has recently been suggested by Turner et al. (Cell 1994. 77: 297) that the complex changes in gene activities accompanying high levels of immunoglobulin secretion are under the common control of a master regulator, Blimp‐1 (B lymphocyte‐induced maturation protein). We show here that in naive mouse B cells stimulated with lipopolysaccharide (LPS) alone (which leads to high IgM production), Blimp‐1 is highly expressed, while cells co‐stimulated with LPS and anti‐μ F(ab′)2 show low levels of Blimp‐1 mRNA and no longer secrete Ig. Iγ1 sterile transcripts are, however, up‐regulated after receptor co‐ligation. Addition of interleukin (IL)‐2 and IL‐5 to LPS + anti‐μ F(ab′)2‐treated primary B cells led to up‐regulation of Blimp‐1 and IgM secretion. Transfection of a Blimp‐1 expression vector also induced IgM secretion. The data indicate that Blimp‐1 is an important regulator of immunoglobulin secretion by primary B cells, and suggest that its level of expression may determine the differentiation to Ig‐secreting plasma cells or entrance and maintenance in the memory pool.
Early development and progression of lymphocyte‐stimulatory cross‐reactive idiotypes expressed on antibodies to soluble egg antigens during Schistosoma mansoni infection of mice
Authors: Bosshardt Stephen C. , Nix Nancy A. , Colley Daniel G. 
Published: March 2007

AbstractIdiotypes (Id) that stimulate immunoregulatory anti‐Id T lymphocyte proliferation are expressed on murine and human antibodies (Ab) to soluble egg antigens (SEA) of Schistosoma mansoni. Kinetics of early expression of these stimulatory Id have now been studied using immunoaffinity‐purified serum anti‐SEA Ab from mice infected with S. mansoni for 6, 7, 8, 12, or 16 weeks. Rabbit anti‐Id Ab specific for mouse anti‐SEA Id expressed at 8 weeks post‐infection (anti‐8WkId) demonstrated the strongest interactions with Id present at 7 and 8 weeks post‐infection by competitive enzyme‐linked immunosorbent assay. Anti‐8WkId Ab reacted progressively less well with 12WkId, 6WkId, and 16WkId. Splenocytes from mice infected for 8 weeks demonstrated the highest blast transformation responses in vitro to anti‐SEA Id from mice infected for 6 weeks, while 7, 8, 12, and 16 weeks post‐infection Id preparations stimulated progressively less proliferation. These data indicate that although eventual Id‐associated immunoregulatory events contribute to chronicity in this disease, production of anti‐SEA Ab that express stimulatory cross‐reactive immunoregulatory Id comprises a substantial portion of the initial, acute anti‐SEA response in mice infected with Schistosoma mansoni. Furthermore, either this particular Id‐expressing response is not maintained, or its proportional presence is greatly diminished by the cumulative production of other multiple anti‐SEA Ab during the establishment of chronicity, perhaps in response to its immunoregulatory influence very early in infection.
TAP1‐deficient mice select a CD8+ T cell repertoire that displays both diversity and peptide specificity
Authors: Sandberg Johan K. , Chambers Benedict J. , Van Kaer Luc , Kärre Klas , Ljunggren Hans‐Gustaf 
Published: March 2007

AbstractMice deficient in the gene encoding the transporter associated with antigen processing 1 (TAP1) are defective in providing major histocompatibility complex (MHC) class I molecules with cytosolic peptides. Consequently, these mice express reduced levels of MHC class I glycoproteins on the cell surface, and have reduced numbers of CD8+ T cells in the periphery. In the present study, we have addressed the diversity and specificity of the peripheral CD8+ T cell population in TAP1 ‐/‐ mice. CD8+ T cells were polyclonal with regard to T cell receptor (TCR) Vβ expression. Overall, Vβ usage in TAP1 ‐/‐ mice appeared to be very similar to that in wild‐type mice, with significantly reduced levels of Vβ5.1/5.2‐expressing CD8+ T cells as the only clear exception. This polyclonal population of CD8+ T cells readily mounted epitope‐specific CTL responses against four out of five well‐defined MHC class I‐restricted peptides. In contrast to allospecific CTL, peptide‐specific CTL from TAP1 ‐/‐ mice did not cross‐react on cells expressing normal levels of H‐2b class I. The present results demonstrate that a polyclonal CD8+ T cell repertoire, displaying both diversity and peptide specificity, is positively selected in mice devoid of a functional peptide transporter. These observations imply that TAP‐dependent peptides are not absolutely required for positive selection of a functionally diverse repertoire of CD8+ T cells.
CC chemokines induce the generation of killer cells from CD56+ cells
Authors: Maghazachi Azzam A. , Al‐Aoukaty Ala , Schall Thomas J. 
Published: March 2007

AbstractWe describe here that members of the CC chemokines exhibit biological activities other than chemotaxis. Macrophage inflammatory protein (MIP)‐1α, MIP‐1β, monocyte chemoattractant protein‐1 and RANTES, but not interleukin (IL)‐8, induce the generation of cytolytic cells, designated here as CHAK (CC chemokine‐activated killer) cells to distinguish them from IL‐2‐activated (LAK) cells. Like IL‐2, CC chemokines can induce the proliferation and activation of killer cells. While incubating CC chemokines with CD4+ or CD8+ cells did not generate CHAK activity, all CC chemokines were capable of inducing CHAK activity upon incubating with CD56+ cells, suggesting that the primary effectors are NK cells. However, the presence of other cell types, such as CD4+ or CD8+, are necessary to induce the proliferation of CD56+ cells. Confirming the involvement of T cell‐derived factors in inducing the proliferation of these cells, anti‐IL‐2 and anti‐interferon‐γ, but not anti‐IL‐1β, anti‐tumor necrosis factor‐α, anti‐IL‐8, or anti‐granulocyte/monocyte‐colony‐stimulating factor inhibited RANTES‐induced proliferation of nylon wool column‐nonadherent cells. Our results may have important clinical applications for the utilization of CHAK cells in the treatment of cancer and immunodeficient patients.
CD8/CD4 lineage commitment occurs by an instructional/default process followed by positive selection
Authors: Benveniste Patricia , Knowles Gisele , Cohen Amos 
Published: March 2007

AbstractIn the present study, we investigated the developmental potential of purified populations of transitional CD4in CD8hi and CD4hi CD8in thymocytes that were further defined according to their differentiation stage by their levels of T cell receptor (TCR) expression into TCRlo, TCRin and TCRhi subpopulations. The differentiation potential of each of these subsets was tested in vitro in a single‐cell suspension culture assay that showed that CD4in CD8hi TCRhi are precursors of CD8 single‐positive cells, whereas CD4hi CD8in TCRin/hi are precursors of both CD4 and CD8 single‐positive thymocytes. The analysis of transitional subsets in mutant mice for either β2‐microglobulin or major histocompatibility complex (MHC) class II further revealed that lineage commitment to the CD8 lineage requires a TCR‐MHC class I engagement, presumably at the immature double‐positive stage of thymic development, while CD4 commitment does not require an MHC class II‐mediated signal, but rather occurs by default. Using the addition of MHC class I‐ or class II‐expressing cells or the addition of total thymocytes to purified sorted transitional precursors for the duration of the cultures in vitro, we identified an additional stage of differentiation for both CD4 and CD8 lineages that requires a positive selection signal. Examination of protein tyrosine phosphorylation of transitional precursors revealed that CD4in CD8hi transitional cells contain a high level of a 70‐kDa phosphorylated protein consistent with a role for ZAP70 in the signal transduction during the positive selection of CD8+ cells.
Inhibition of thymocyte negative selection by T cell receptor antagonist peptides
Authors: Williams Owen , Tanaka Yujiro , Bix Mark , Murdjeva Marianna , Littman Dan R. , Kioussis Dimitris 
Published: March 2007

AbstractThe T cell receptor (TCR) recognizes antigenic peptide presented by major histocompatibility complex (MHC) molecules. Analogs of antigenic peptides have been shown to inhibit antigen‐specific T cell responses, a phenomenon described as TCR antagonism. We have examined the effect of a natural variant of an antigenic peptide and a synthetic peptide analog, on the responses of mature T cells and immature thymocytes from an αβ TCR‐transgenic mouse (F5), the TCR of which recognizes a nonamer peptide from the nucleoprotein (NP) of influenza virus in the context of the H‐2Db MHC molecule. Both peptides were shown to antagonize specifically the T cell cytolytic response without being able directly to stimulate mature T cells from these transgenic mice. Furthermore, a negative selection assay in vitro was used to demonstrate for the first time that antagonistic peptides are capable of antagonizing thymocyte deletion induced by antigenic peptides. These data suggest that the final selection of a T cell could be the result of a balance between the positive and negative influences of endogenous peptide ligands.
Interleukin‐13 is produced by activated human CD45RA+ and CD45R0+ T cells: modulation by interleukin‐4 and interleukin‐12
Authors: Jung Thomas , Wijdenes John , Neumann Christine , de Vries Jan E. , Yssel Hans 
Published: March 2007

AbstractInterleukin (IL)‐13 is a cytokine originally identified as a product of activated T cells. Little is known, however, about IL‐13 production by human T cells and its modulation by other cytokines. Here, we show that IL‐13 is produced by activated human CD4+ and CD8+ CD45R0+ memory T cells and CD4+ and CD8+ CD45RA+ naive T cells. In contrast, IL‐4, which shares many biological activities with IL‐13, is only produced by CD45R0+ T cells following activation. Analysis of intracellular cytokine production by single CD45RA+ and CD45R0+ T cells indicated that IL‐13 continued to be produced for more than 24 h after stimulation, whereas IL‐4 could not be detected after 24 h. These data were confirmed by measurement of specific mRNA and suggest that IL‐13, unlike IL‐4, but like interferon‐γ (IFN‐γ), is a cytokine with long‐lasting kinetics. The majority of human CD45R0+ T cells produced IL‐4 and IL‐13 simultaneously. In contrast, IFN‐γ protein was generally not co‐expressed with IL‐4 or IL‐13. IL‐4 added to primary cultures of highly purified peripheral blood T cells activated by the combination of anti‐CD3+anti‐CD28 mAb enhanced IL‐13 production by CD45RA+ and to a lesser extent by CD45R0+ T cells. Under these conditions, however, IL‐12 inhibited IL‐13 production by CD45RA+ T cells and to a lesser extent by CD45R0+ T cells in a dose‐dependent fashion. These inhibiting effects were not related to enhanced IFN‐γ production induced by IL‐12, since IFN‐γ by itself did not affect IL‐13 production. Collectively, our data indicate that IL‐13 is produced by peripheral blood T cells which also produce IL‐4, but not IFN‐γ, and by naive CD45RA+ T cells which, in contrast, fail to produce IL‐4. These observations, together with the long‐lasting production of IL‐13, suggest that IL‐13 may have IL‐4‐like functions in situations where T cell‐derived IL‐4 is still absent or where its production has already been down‐regulated.
The Jβ segment of the T cell receptor contributes to the Vβ‐specific T cell expansion caused by staphylococcal enterotoxin B and Urtica dioica superantigens
Authors: Musette Philippe , Galelli Anne , Truffa‐Bachi Paolo , Peumans Willy , Kourilsky Philippe , Gachelin Gabriel 
Published: March 2007

AbstractWe have used a new polymerase chain reaction‐based technique to analyze at the clonal level the CDR3 diversity and the Jβ usage associated with the Vβ‐dependent T cell receptor (TCR) recognition of two superantigens: the staphylococcal enterotoxin B and the Urtica dioica agglutinin. Our results show that a subset of Jβ elements is preferentially expanded in a given Vβ family, independently of the nature of the superantigen. By contrast, the CDR3 loop does not contribute significantly to the T cell expansion induced by the superantigens. We conclude that the Jβ segment of the TCR β chain, but not the CDR3 region, participates in superantigen binding, presumably by influencing the quaternary structure of the TCR β chain.