bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD45‐mediated regulation of LFA1 function in human natural killer cells. Anti‐CD45 monoclonal antibodies inhibit the calcium mobilization induced via LFA1 molecules
Authors: Poggi Alessandro , Pardi Ruggero , Pella Nicoletta , Morelli Luigia , Sivori Simona , Vitale Massimo , Revello Valentino , Moretta Alessandro , Moretta Lorenzo 
Published: March 2007

AbstractThe TA218 and T205 monoclonal antibodies (mAb) were selected on the basis of their ability to inhibit the non‐major histocompatibility complex‐restricted lysis of the murine mastocytoma P815 cell line mediated by CD3−CD16+ natural killer (NK) cells. Both mAb were found to react with CD45 molecules, as demonstrated by immunoprecipitation after surface iodination and western blot analysis. A panel of tumor target cells susceptible to lysis by polyclonal or clonal CD3−CD16+ NK cells was used to study the mAb‐mediated inhibitory effect. The inhibition of cytolysis mediated by TA218 and T205 mAb was found to consistently parralel the inhibition mediated (with the same tumor target cells) by the anti‐LFAlα mAb TS.1.22 or by the anti‐LFA1β mAb TS.1.18. However, different from the anti‐LFAl mAb, T205 or TA218 mAb did not inhibit the binding of activated CD3−CD16+ effector NK cells to the same tumor target cells. This finding supported the concept that the anti‐CD45 mAb‐mediated inhibition could occur at a post‐binding stage. In polyclonal or clonal CD3‐CD16+ NK cellsT205 orTA218 mAb were found to reduce by 50–70 % the intracellular Ca++ ([Ca++]i) mobilization induced by anti‐LFAlα or anti‐LFA1β mAb. On the other hand, TA218 and T205 mAb did not inhibit the Ca++ mobilization induced by anti‐CD 16 mAb or phytohemagglutinin, thus suggesting that, in NK cells, CD45 molecules may exert a selective inhibitory effect on the signal transduction mediated by LFA1 molecules. In line with this hypothesis, the cytolytic activity of human NK clones was triggered in the presence of the hybridoma cells secreting either anti‐CD16 or anti‐LFAla mAb (as “triggering targets”). This effect of anti‐LFAlα, but not of anti‐CD16 hybridoma was susceptible to inhibition by the anti‐CD45 mAb T205 or TA218. Further, experiments on cloned NK cells indicated that T205 or TA218 mAb induced a strong decrease in the constitutive phosphorylation of the LFAlα chain (but not of HLA class I antigens). Taken together, these studies suggest that in human NK lymphocytes, CD45 molecule may regulate both the activation state and the function of the LFA1 molecule.
Murine platelet endothelial cell adhesion molecule (PECAM‐1)/CD31 modulates β2 integrins on lymphokine‐activated killer cells
Authors: Piali Luca , Albelda Steven M. , Scott Baldwin H. , Hammel Philippe , Gisler Roland H. , Imhof Beat A. 
Published: March 2007

AbstractLymphokine‐activated killer (LAK) cells are able to colonize sites of tumor lesions in mouse and man. The molecular mechanisms of homing in on tumors are largely unknown. However, before LAK cells can reach the tumor, they must adhere to the vascular endothelia within the lesion and then extravasate. We developed a novel mAb, EA‐3, which recognizes the murine homologue of the human adhesion molecule CD31. It is present on a subpopulation of murine LAK cells and all endothelial cells. CD31 was also involved in the adhesion of LAK cells to endothelium. Since CD31 can initiate integrin activation by inside‐out signaling after binding to its ligand, EA‐3 was used to minimic this in adhesion assays. It induces modifications in the β2 integrin LFA‐1, leading to increased binding capacities of the cells to endothelium. In contrast, β1 integrins and RGD‐binding integrins were not affected. These results suggest that expression of CD31 might confer adhesive advantages for LAK cells prone to tumor infiltration.
Regulation of CD59 expression on the human endothelial cell line EA.hy 926
Authors: Meri Seppo , Mattila Pirkko , Renkonen Risto 
Published: March 2007

AbstractCD59 (protectin) is an 18–20‐kDa inhibitor of the membrane attack complex of complement. It protects homologous cells from complement‐mediated damage and has been shown to be present on the endothelial cell membranes both in vitro and in vivo. In this study we observed that the surface expression of CD59 on the cultured EA.hy 926 endothelial cell line can be up‐regulated to an approximately threefold higher level after a 72‐h stimulation by the protein kinase C inducers phorbol‐12‐myristate‐13 acetate (PMA; 10 nM) and calcium ionophore, A23187 (100 nM). Similarly, an increase in the level of CD59 expression was seen by the protein kinase A inducer dibutyryl‐cyclic adenosine monophosphate. In Northern blot analysis increases were observed in CD59 mRNA expression, particularly in the level of the longest 1.9‐kb, 2.1‐kb and 5.8‐kb transcripts. A functional significance for the increased CD59 expression was implied by an observed increased resistance of the PMA‐stimulated EA.hy 926 cells to complement‐mediated cell lysis.
The association of the protein tyrosine kinases p56lck and p60fyn with the glycosyl phosphatidylinositol‐anchored proteins Thy‐1 and CD48 in rat thymocytes is dependent on the state of cellular activation
Authors: Garnett David , Neil Barclay A. , Carmo Alexandre M. , Beyers Albertus D. 
Published: March 2007

AbstractCell surface glycoproteins anchored to the plasma membrane via glycosyl‐phosphatidylinositol (GPI) structures, and hence having no cytoplasmic domains, can nevertheless transmit activation signals in lymphocytes. By immunoprecipitation from detergent lysates and in vitro immune complex kinase reactions the GPI‐anchored molecules Thy‐1 and CD48 are shown to be associated with multimolecular complexes of phosphoproteins including the protein tyrosine kinases p56lck: and p60fyn in both rat and mouse thymocytes. Moreover, the kinase activity associated with Thy‐1 on rat thymocytes is shown to be dependent on the activation state of the cells, with stimulation by the lectin, concanavalin A, producing a marked decrease in Thy‐1‐associated kinase activity. In such activated cells, there is an increased association of kinase activity with CD48, but this may be explained in terms of increased surface expression of CD48 and of increased total kinase activity. Additional phosphoproteins of 85, 36 and 32 kDa were consistently seen as components of the complexes.
Dynamic response of murine gut intraepithelial T cells after infection by the coccidian parasite Eimeria
Authors: Craig Findly R. , Roberts Scott J. , Hayday Adrian C. 
Published: March 2007

AbstractThe response of murine intraepithelial lymphocyte (IEL) populations to challenge by Eimeria vermiformis, a naturally occurring protozoan parasite of the gut epithelium, has been studied. The number of recoverable IEL increased within 3 days post infection, was depleted by day 7 post infection, but was significantly increased again by about day 14 post infection. Special attention was paid to γ δ+ IEL T cells, because they are of unknown functions. These cells showed changes in numbers similar to the total IEL population. Moreover, by day 3, increased expression was detected among γ δ + IEL T cells, of T cell receptor genes not constitutively associated with the intestine. These results demonstrate that the IEL repertoire, and within that, the γ δ + T cell repertoire, can be extremely dynamic post infection with a naturally occurring epithelial‐tropic pathogen. In considering the potential benefits of such IEL changes, we hypothesize that they may be relevant to the transient protection of the host's epithelium, both from parasitic re‐infection, and from potentially damaging inflammation.
Endogenous retroviral superantigen presentation by B cells induces the development of type 1 CD4+ T helper lymphocytes
Authors: Gollob Kenneth J. , Nagelkerken Lex , Coffman Robert L. 
Published: March 2007

AbstractThe endogenous retroviral superantigen, minor lymphocyte stimulating antigen (Mls 1a, encoded by Mtv‐7), when presented by highly purified B cells induced the development of a highly polarized population of T helper (Th)1 cells from naive peripheral CD4+ T cells in vitro. Immobilized anti‐Vβb6+ antibodies similarly generated highly polarized, largely Vβ6+, Th 1 populations in vitro. In the presence of exogenous interleukin‐4, both stimuli were capable of generating Th 2, rather than Th 1 populations. Mls 1a presentation by B cells in vivo led to the development of an equally polarized Th 1 population. Using monoclonal antibodies against interferon‐γ and transforming growth factor‐β it was demonstrated that maximal Th 1 development with either stimulus in vitro was dependent on the endogenous production of these two cytokines. Thus, our results demonstrate that the retroviral encoded superantigen, Mls 1a, drives the development of Th 1 cells both in vitro and in vivo, and they suggest that B cell presentation does not, in itself, lead to the generation of Th 2 cells.
Ligation of CD28 receptor by B7 induces formation of D‐3 phosphoinositides in T lymphocytes independently of T cell receptor/CD3 activation
Authors: Ward Stephen G. , Westwick John , Hall Nicolas D. , Sansom David M. 
Published: March 2007

AbstractThe co‐stimulatory role of B7/CD28 interactions is important in promoting T cell activation. Very little is known about the intracellular events that follow CD28 engagement although recent evidence has implicated coupling of CD28 to a protein tyrosine kinase signal transduction pathway. In this study we have investigated the putative role of D‐3 phosphoinositides as mediators of CD28 receptor signaling, since phosphoinositide (PI) 3‐kinase, the enzyme responsible for D‐3 phosphoinositide formation, is a known substrate for protein tyrosine kinases associated with certain T cell surface receptors such as CD4 and interleukin‐2 receptor. The lipid products of PI 3‐kinase activity have been suggested to play a role in mitogenic signaling and growth regulation in other cells. Chinese hamster ovary cells (CHO) previously transfected with B7 cDNA, induced time‐dependent elevation above basal levels of phosphatidylinositol(3,4)‐bisphosphate (PtdIns(3,4)P2) and PtdIns(3,4,5)P3, while parental CHO cells that did not express B7 had no effect on these lipids. Moreover, the elevation of these same lipids by CD3 ligation was potentiated in an additive manner by CHO‐B7+ but not by CHO‐B7− cells. CHO‐B7+ and CHO‐B7− cells did not activate phospholipase C as evidenced by their inability to modulate basal or CD3‐induced changes in the levels of phosphatidic acid or D‐4 and D‐5 phosphoinositides. These data imply that PI 3‐kinase but not phospholipase C, may be an important signal transduction molecule with respect to CD28‐mediated co‐stimulation and T cell activation following ligation by B7.
T cell development in a major histocompatibility complex class II‐deficient patient
Authors: Van Eggermond Marja C. J. A. , Rijkers Ger T. , Kuis Wietse , Zegers Ben J. M. , van den Elsen Peter J. 
Published: March 2007

AbstractIn this report we show that the major histocompatibility complex (MHC) class II‐negative thymus of a bare lymphocyte syndrome (BLS) patient contains a reduced CD4+ CD8− T cell population when compared to thymocytes derived from a MHC class II‐expressing thymus. Of these CD4+ CD8− BLS thymocytes, approximately only one third co‐expressed the CD3 antigen, moreover at a lower expression level when compared to control thymocytes. This suggests a partial maturation of the CD4+ CD8− T cells in the absence of MHC class II expression. Among the BLS thymocytes, CD4+ CD8+ thymocytes could easily be detected. Noteworthy, the number of CD4− CD8+ thymocytes was significantly increased. CD4+ CD8− T cells could also be found among the BLS peripheral blood mononuclear cells, albeit at reduced numbers. Despite the absence of peripheral MHC class II expression, the majority of these CD4+ CD8− T cells co‐expressed the CD45RO marker. In the BLS patient, thymocytes as well as peripheral CD4+ CD8− T cells were not restricted in the use of the available T cell receptor (TcR) V gene family pool. However, the lack of detectable levels of thymic and peripheral MHC class II antigen expression in the BLS patient had altered the CD4−skewing patterns of TcR V gene families which were present in normal individuals. In conclusion, the lack of MHC class II expression in the BLS patient does not completely inhibit the CD4+ CD8− T cell development.
Viral hemagglutinin augments peptide‐specific cytotoxic T cell responses
Authors: Ertel Christian , Millar Neil S. , Emmerson Peter T. , Schirrmacher Volker , Von Hoegen Paul 
Published: March 2007

AbstractIn attempt to increase the induction of peptide‐specific cytolytic T cells (CTL) we investigated the effect of the Newcastle disease virus (NDV) hemagglutinin‐neuraminidase (HN) gene product on the activation of peptide‐specific CTL. Spleen cells of CH3 mice immunized against the influenza nucleoprotein peptide 50–63 (NP 50–63) were restimulated in vitro (i) with peptide‐pulsed syngeneic fibroblast cells (Ltk−) as antigen‐presenting cells, which were in addition (ii) infected with NDV or (iii) stably transfected with the HN cDN A of NDV. A greater than sixfold increase in peptide‐specific CTL responses was observed in cultures restimulated with peptide‐pulsed Ltk− cells which co‐expressed viral hemagglutinin due to either infection or transfection.A similar augmentation was seen in CTL responses against other types of antigen (major histocompatibility complex alloantigens, minor histocompatibility antigens or tumor antigens) when suboptimal cultures were stimulated with the respective antigen‐presenting cells modified by NDV infection. These findings suggest that NDV or viral HN expressed on antigen‐presenting cells or tumor cells can exert a T cell co‐stimulatory function.
An age‐related γδ T cell suppressor activity correlates with the outcome of autoimmunity in experimental Trypanosoma cruzi infection
Authors: Cardillo Fabíola , Falcao Roberto P. , Rossi Marcos A. , Mengel José 
Published: March 2007

AbstractIn this work the suppressive activity of splenic T cells from young and aged BALB/c mice infected with Trypanosoma cruzi were compared and correlated with the development of autoimmune myocarditis. The T cells from young adult BALB/c mice with acute T. cruzi infection exhibit suppressor activity when added to full allogeneic or Mis‐disparate mixed lymphocyte cultures. This suppression could not be reverted by exogenous interleukin (IL)‐2 and was not directly dependent on the presence of IL‐4, IL‐10 or transforming growth factor‐β. Further characterization of the T cell lineage responsible for the suppressor activity by in vitro and/or in vivo depletion with monoclonal antibody to αβ or γδ T cell receptor revealed that splenic γδ T cells function as suppressor lymphocytes in young T. cruzi‐infected mice. In addition, these young adult BALB/c mice do not develop autoimmune myocarditis and showed a low incidence of syngeneic heart graft rejection in the early chronic phase of the infection. In contrast, T cells from acutely infected aged BALB/c mice lacked demonstrable T suppressor activity. Furthermore, these mice developed a severe autoimmune myocarditis as early as 2 months after the onset of the infection, when the majority of them reject syngeneic heart grafts. These findings suggest that a γδ T cell‐mediated suppressor mechanism may operate in the avoidance of the breaking of tissue‐specific tolerance during the acute infection. Moreover, such a mechanism is likely related to the immune system chronobiology.
Molecular cloning of a ligand for the inducible T cell gene 4‐1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor
Authors: Goodwin Raymond G. , Din Wenie S. , Davis‐Smith Terri , Anderson Dirk M. , Gimpel Steven D. , Sato Timothy A. , Maliszewski Charles R. , Brannan Camilynn I. , Copeland Neal G. , Jenkins Nancy A. , Farrah Terry , Armitage Richard J. , Fanslow William C. , Smith Craig A. 
Published: March 2007

Abstract4‐1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4‐1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4‐1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. The gene for 4‐IBB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the gene for CD30. The gene for 4‐IBB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4‐1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4‐1BB.
Clonal anergy to staphylococcal enterotoxin B in vivo: selective effects on T cell subsets and lymphokines
Authors: Baschieri Selene , Lees Rosemary K. , Lussow Alexander R. , Robson MacDonald H. 
Published: March 2007

AbstractInjection of bacterial superantigens such as staphylococcal enterotoxin B (SEB) in adult mice results in initial proliferation of SEB‐responsive Vβ8+ T cells followed by induction of a state of non‐responsiveness frequently referred to as clonal anergy. We show here that SEB‐induced anergy involves selective changes in lymphokine production and that it affects CD4+ Vβ 8+ and CD8+ Vβ 8+ T cells in different fashions. Whereas both CD4+ Vβ 8+ and CD8+ Vβ 8+ cells from anergic mice exhibit strongly reduced proliferative capacity and interleukin(IL)‐2 production upon restimulation with SEB either in vivo or in vitro the CD8+ subset from SEB‐injected mice produces other lymphokines (such as interferon(IFN)‐γ) at normal or slightly increased levels in response to SEB. Changes in the levels of production of IL‐2 and IFN‐γ protein correlated well with mRNA accumulation both in vivo and in vitro. Collectively these data suggest that superantigen‐induced anergy involves selective changes in signal transduction and/or gene regulation in T lymphocytes.
Chimaeric anti‐CD4 monoclonal antibody cross‐linked by monocyte Fcγ receptor mediates apoptosis of human CD4 lymphocytes
Authors: Choy Ernest H. S. , Adjaye James , Forrest Lesley , Kingsley Gabrielle H. , Panayi Gabriel S. 
Published: March 2007

AbstractPrevious studies have shown that murine anti‐CD4 monoclonal antibody, cross‐linked by rabbit anti‐mouse immunoglobulin, could mediate apoptosis of murine CD4+ lymphocytes when they were stimulated by T cell receptor antibody. In this study, we have shown that the murine anti‐CD4 monoclonal antibody, OKT4, can induce apoptosis in human CD4+ T cells stimulated by the recall antigen tuberculin purified protein derivative (PPD) only when cross‐linked by rabbit anti‐mouse immunoglobulin. The chimeric anti‐CD4 monoclonal antibody, cM‐T412 whose Fc fragment is human, was able to cause apoptosis without cross‐linking by a second antibody. Similarly, abolition of PPD‐induced proliferation of peripheral blood mononuclear cells by cM‐T412 did not require cross‐linking with rabbit anti‐human immunoglobulin. Inhibition of proliferation by cM‐T412 could be reduced by pre‐treating monocytes with heat‐aggregated human IgG. This suggested that monocyte Fcγ receptors might be cross‐linking the human Fc of cM‐T412. Propidium iodide staining together with immunofluorescence showed that the apoptotic cells were indeed CD4+ lymphocytes. It is proposed that during treatment with cM‐T412 in autoimmune disease such as rheumatoid arthritis, cM‐T412‐coated CD4 T cells, when they are subsequently stimulated by the unknown arthritogenic antigen, may undergo apoptotic cell death through cross‐linking of cM‐T412 on Fey receptor‐positive cells within the joint.
Regional sublocalization of the human CD69 gene to chromosome bands 12p12.3‐p13.2, the predicted region of the human natural killer cell gene complex
Authors: Schnittger Susanne , Hamann Jörg , Dannenberg Christine , Fiebig Helmut , Strauss Michael , Fonatsch Christa 
Published: March 2007

AbstractThe early activation antigen CD69 is a member of a supergene family of type II integral membrane proteins with a C‐type lectin domain. In recent reports the genes encoding the natural killer (NK) cell‐related molecules of this supergene family, NKR‐P1, NK1.1 and Ly‐49, were shown to be clustered in a chromosomal region in mouse, termed the NK gene complex. The human homologue of this complex is likely to reside on chromosome 12 near the PRP locus (12p13.2). By analyzing T cell hybrids, the CD69 gene was previously mapped to human chromosome 12. Here we report the regional sublocalization of the human CD69 gene to chromosome bands 12p12.3‐p13.2, suggesting that CD69 belongs to one linkage group together with different cell surface molecules on NK cells.
Mouse intestinal epithelial cells express the self superantigen Mis1
Authors: Kaiserlian Dominique , Vidal Karine , Robson MacDonald H. , Grosjean Isabelle 
Published: March 2007

AbstractIn previous studies, we demonstrated that intestinal epithelial cells of the mouse small intestine could present exogenous antigen to specific CD4+ T cell hybridomas. We now report on the abililty of normal enterocytes to present the self superantigen M1sla. Enterocytes from M1sla but not from M1slb strains stimulated interleukin‐2 production through aVβ6+ T cell hybridoma specific for M1sla determinants. Antibody inhibition experiments showed that enterocytes presented M is determinants via a major histocompatibility complex class II‐dependent mechanism. Furthermore, the ability of enterocytes to activate Vβ6+ M1sla‐specific T cells was inhibited by monoclonal antibodies against the Orf protein encoded by an Mtv‐7 provirus which is associated with M1sla expression. These findings provide evidence for the first time that M is determinants are expressed on normal enterocytes and support the theory of a possible role of these cells in extrathymic selection of T cell receptor Vβ repertoire of intraepithelial T lymphocytes.
CD21 expressed on basophilic cells is involved in histamine release triggered by CD23 and anti‐CD21 antibodies
Authors: Bacon Kevin , Gauchat Jean‐Francois , Aubry Jean‐Pierre , Pochon Sibylle , Graber Pierre , Henchoz Sybille , Bonnefoy Jean‐Yves 
Published: March 2007

AbstractRecombinant full‐length human CD23 incorporated into fluorescent liposomes was used to detect a ligand for CD23 on the basophilic leukemia cell line, KU 812. Based on our recent finding that CD23 interacts with CD21 on subsets of B and T cells, we investigated if the same ligand was involved on KU 812 cells. An anti‐CD21 monoclonal antibody (mAb) BU‐33, was able to totally block CD23‐liposome binding to KU 812 cells. Moreover, KU 812 cells express CD21 mRNA and have a cell surface molecule that reacts with anti‐CD21 mAb. The CD23/CD21 interaction was not merely physical but was also associated with an increase in histamine release by KU 812 cells. Both recombinant soluble CD23 and an anti‐CD21 mAb increased histamine release by KU 812 cells. The CD23 and anti‐CD21 mAb‐mediated effect on histamine release was not restricted to the leukemic cell line, but was also observed with normal human blood basophils. These data demonstrate that CD21 is expressed on basophilic cells and that CD21 controls histamine production upon ligand‐induced stimulation (CD23 or anti‐CD21 mAb).