bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of primary anti‐viral cytotoxic T cells by in vitro stimulation with short synthetic peptide and interleukin‐7
Authors: Kos Ferdynand J. , Müllbacher Arno 
Published: March 2007

AbstractThe present study investigated whether a short synthetic peptide NPP, with a modified sequence (147–158 R156−) derived from influenza A virus nucleoprotein with high affinity for Kd major histocompatibillity complex class I molecules, could induce primary influenza virus‐specific cytotoxic T (Tc) cells in vitro. Naive BALB/c (H‐2d) splenocytes did not respond to the stimulation with only NPP with the generation of effector Tc cells specific for influenza A virus‐infected target cells in vitro. However, they were able to do so if cultured with NPP in the presence of IL‐7. IL‐7 activity in this system differed significantly from IL‐2 activity in the specificity of the effect. The use of exogenous IL‐2, instead of IL‐7, with NPP resulted in the induction of lytic cells that lysed both influenza virus‐infected and uninfected syngeneic target cells. These results suggest that IL‐7 is a potent regulatory cytokine in the antigen‐specific activation of resting naive Tc cell precursors and may provide the necessary conditions for the induction of human primary Tc cells in vitro.
Cloning of TRAP, a ligand for CD40 on human T cells
Authors: Graf Daniel , Korthäuer Ulf , Mages Hans W. , Senger Gabriele , Kroczek Richard A. 
Published: March 2007

AbstractA cDNA clone, designated TRAP (TNF‐related activation protein) was isolated from a collection of T cell activation genes. The polypeptide encoded by a mRNA of approx. 2.3 kb is 261 amino acids long with a calculated Mr of 29.3 kDa. The structural features predict a type II transmembrane protein, but are also compatible with a secreted form. TRAP is highly similar to an identified murine CD40 ligand both at the cDNA (82.8% identity) and the protein (77.4% identity) levels, and related to tumor necrosis factor/lymphotoxin. Expressed in a murine myeloma, TRAP was identified as a ligand for CD40 by binding to a soluble CD40 construct. TRAP mRNA is expressed in a T cell‐specific fashion with a maximum at 8 h after stimulation. The TRAP gene is located in the q26.3–q27.1 region of the X chromosome.
T helper type 2‐like cells and therapeutic effects of interferon‐γ in combined immunodeficiency with hypereosinophilia (Omenn's syndrome)
Authors: Schandené Liliane , Ferster Alina , Mascart‐Lemone Françoise , Crusiaux Alain , Gérard Catherine , Marchant Arnaud , Lybin Myriam , Velu Thierry , Sariban Eric , Goldman Michel 
Published: March 2007

AbstractWe characterized the defects of CD4+ cells in a 17‐month‐old girl suffering from combined immunodeficiency with hypereosinophilia (Omenn's syndrome). Because the vast majority of peripheral blood CD4+ cells expressed the CD45R0 isoform, we purified circulating CD4+ CD45R0+ cells from the patient and healthy individuals in order to compare their production of cytokines. The patient's CD4+ CD45R0+ cells spontaneously produced high levels of interleukin‐5 (IL‐5) in vitro (1600 pg/ml after 24 h of culture) and this was associated with the presence of IL‐5 in serum (323 pg/ml). After stimulation with phorbol 12‐myristate 13‐acetate (PMA) and calcium ionophore A23187, they produced higher levels of IL‐4 (306 vs. 55 ± 4 pg/ml) and IL‐5 (2900 vs. 213 ± 72 pg/ml) and lower levels of IL‐2 (17 vs. 63 ± 17 IU/ml) and interferon‐γ (IFN‐γ) (16 vs. 299 ± 70 IU/ml) than controls CD4+ CD45R0+ cells. This T helper type 2 (Th2) pattern was confirmed by the detection using reverse polymerase chain reaction of IL‐4, IL‐5 and IL‐10 mRNA within peripheral blood mononuclear cells. During a therapeutic trial with human IFN‐γ (40 μg/day) which ameliorated the clinical status of the patient, we observed a down‐regulation of the in vivo expression of IL‐5 and IL‐10, a normalization of the eosinophil count and an improvement of the Tcell response to phytohemagglutinin. This observation indicates for the first time that Th2‐like cells might be involved in certain forms of congenital immunodeficiency and that IFN‐γ might down‐regulate their activities in vivo.
Comparison of three different forms of HLA‐DR4Dw4 proteins
Authors: Buelow Roland , Paborsky Lisa R. , van Schooten Wim C. A. , Kummerehl Tammy J. , Schreifels Robert , Marshall Keith , Mayer John , Rothbard Jonathan B. 
Published: March 2007

AbstractThe biochemical behavior and peptide binding properties of a soluble form of the human class II DR4Dw4 molecule (PI‐DR4Dw4) were compared to DR4Dw4 molecules containing the transmembrane and cytoplasmic domains that were purified both from B and transfected Chinese hamster ovary cells. Recombinant and B cell‐derived DR4Dw4 molecules bound monoclonal anti‐DR4Dw4 antibodies with different affinities and varied in their stability in the presence of sodium dodecyl sulfate. The three forms of DR4Dw4 bound peptides with a similar apparent affinity constant, but soluble class II molecules bound up to ten times more peptide than DR4Dw4 containing a transmembrane region. Peptide binding kinetics for soluble DR4Dw4 molecules were 10‐20 times faster than for the other two forms of DR4Dw4 molecules. Finally, soluble PI‐DR4Dw4/peptide complexes were shown to stimulate T cell proliferation.
Inhibition of activation‐induced changes in the structure of the T cell interleukin‐7 receptor by cyclosporin A and FK506
Authors: Foxwell Brian M. J. , L. Willcocks Joanie , Taylor‐Fishwick David A. , Kulig Kimary , Ryffel Bernhard , Londei Marco 
Published: March 2007

AbstractWe have recently shown that activation of T cells causes structural changes in the interleukin‐7 receptor (IL‐7R) (Foxwell et al. Int. Immunol. 1992. 4: 277). Unactivated cells expressed a receptor characterized as a cross‐linked protein of 107‐kDa whereas activated cells had reduced levels of this 107‐kDa complex and now express a major cross‐linked product of 93 kDa. These changes in receptor expression were concomitant with the acquisition of IL‐7 growth responsiveness by activated T cells. In this study, the effect of the potent immunosuppressive agents cyclosporin A and FK506 on the activation‐induced responsiveness to IL‐7‐driven proliferation and the concomitant changes in receptor structure have been investigated. Cyclosporin A and FK506 suppressed the expression of the 93‐kDa complex and the loss of the 107‐kDa complex on activated cells. The presence of exogenous IL‐7 inhibited the effects of the drugs on IL‐7R structure, allowing expression of the 93‐kDa complex. Expression of the 93‐kDa complex could also be induced either by ionomycin or phorbol esters. As observed for other T cell activation parameters, only those which induced a calcium signal (ionomycin) but not protein kinase C (phorbol esters) were sensitive to the drugs. In all studies, the expression of the 93‐kDa complex correlated with the ability of cells to proliferate to IL‐7, and thus these results further support the hypothesis that the 93‐kDa form of the IL‐7R is required to transmit the cytokine's growth signal. Moreover, these data suggest that activation‐induced transcriptional events are required for the expression of the 93‐kDa complex and the down‐regulation of the 107‐kDa complex. As reported for IL‐2R and IL‐4R, our data also show that the expression of another T cell growth factor receptor is sensitive to the effects of cyclosporin A and FK506. These observations also have important implications for reported cyclosporin A effects on the thymus where IL‐7 can act as a growth factor for thymocytes.
Rapid re‐expression of CD45RC on rat CD4 T cells in vitro correlates with a change in function
Authors: Sarawar Sally R. , Sparshott Sheila M. , Sutton Philip , Yang Chun‐Ping , Hutchinson Ian V. , Bell Eric B. 
Published: March 2007

AbstractRat CD4+ T cells are divided phenotypically by the anti‐CD45RC monoclonal antibody OX22 into subsets with contrasting functions. Stimulation of T cells in vitro is known to induce a change in isoform from CD45RC+ to CD45RC−. We have investigated the in vitro conditions which promote a switch in isoform in the opposite direction. We observed that a majority of CD45RC− CD4 T cells (> 90%) spontaneously re‐expressed CD45RC during the first 1‐3 days of culture in both the presence and absence of alloantigen. The T cells remained CD45RC+ when cultured for 7 days in serum‐free growth medium. However, alloantigen‐activated lymphocytes, expressing the interleukin‐2 receptor (IL‐2R), down‐regulated CD45RC by day 4 and remained CD45RC− during the course of the experiment. Using mixtures of allotype‐marked CD45RC+ and CD45RC−T cells, it was demonstrated that each subset showed comparable survival, IL‐2R expression and time courses of activation in response to alloantigen. The repertoire of neither subset was, therefore, deficient in terms of allorecognition. The rapid re‐expression of CD45RC in culture was accompanied by a change in function: CD45RC+ “converts”, obtained by overnight culture of CD45RC− T cells, induced significantly higher graft‐versus‐host responses. Thus, the transition in culture from CD45RC− to CD45RC+ reflects a major functional reprogramming of the cell and not a trivial modulation of a surface antigen.
Protein tyrosine kinases couple the interleukin‐2 receptor to p21ras
Authors: Izquierdo Manuel , Cantrell Doreen A. 
Published: March 2007

AbstractThe T cell growth factor interleukin‐2 (IL‐2) induces p21ras activation in T lymphocytes. We have previously shown that a protein kinase C (PKC)‐mediated pathway for p21ras regulation exists in T cells and that the IL‐2 receptor (IL‐2R) can couple to p21ras independently of the presence of the PKC pathway for p21ras regulation. Our data show that in conditions where cellular protein tyrosine kinases (PTK) were efficiently down‐regulated by pretreatment with the specific PTK inhibitor herbimycin, the IL‐2‐induced activation of p21ras was blocked. Herbimycin did not inhibit the PKC‐mediated pathway for p21ras regulation. Thus, the data indicate that PTK are involved in the coupling of the IL‐2R to p21ras.
Phosphorylation of surface E‐selectin and the effect of soluble ligand (Sialyl Lewisx) on the half‐life of E‐selectin
Authors: Smeets Edgar F. , De Vries Theodora , Leeuwenberg Jet F. M. , van den Eijnden Dirk H. , Buurman Wim A. , Neefjes Jacques J. 
Published: March 2007

AbstractE‐selectin (ELAM‐1) is an adhesion molecule for leukocytes that is transiently expressed on endothelial cells. Following cell surface expression of E‐selectin on human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor, the induced E‐selectin molecules are rapidly degraded. The kinetics of turnover of surface disposed E‐selectin were investigated. The rapid disappearance of surface E‐selectin is temperature dependent and sensitive to the lysosomotropic agent chloroquine. The half‐life of E‐selectin is not affected by inclusion of soluble sialyl Lewis x (sLex) ligands in the medium. Surface E‐selectin is phosphorylated on one or more serine residues, but this modification is not obviously related to internalization.
Regulation of T helper cell cytokine expression: functional dichotomy of antigen‐presenting cells
Authors: Schmitz Jürgen , Assenmacher Mario , Radbruch Andreas 
Published: March 2007

AbstractA bias to either cell‐mediated or antibody‐mediated effector mechanisms is induced in an immune response against a pathogen, if activated T helper cells (Th) predominantly express Th1 [interleukin (IL)‐2, interferon (IFN)‐γ, and tumor necrosis factor (TNF)‐β] or Th2 (IL‐4, IL‐5, IL‐6 and IL‐10) cytokines. Here we provide evidence that, due to the capability to secrete IL‐1, macrophages, but not B cells, as antigen‐presenting cells (APC) induce production of IFN‐γ in resting Th cells. Normal murine splenic Th cells were activated in vitro with the superantigen Staphylococcus aureus enterotoxin B (SEB) presented by macrophages as compared to other APC from murine spleen. As determined by immunofluorescence, Th cells producing IL‐2 but almost none producing IL‐4 and IL‐5 are generated, irrespective of the type of APC. Generation of IFN‐γ‐producing Th cells is largely dependent on presentation of SEB by macrophages. The requirement for macrophages, however, is overcome if IL‐1 is provided. Expression of IFN‐y by Th cells is not induced, if production of IL‐1 by macrophages is inhibited by IL‐10. Our results suggest a functional dichotomy of APC: normal resting Th cells differentiate into IL‐2 and IFN‐γ secreting cells (Th1 cells) if antigen is presented by macrophages, whereas presentation by B cells generates Th cells secreting IL‐2, which might differentiate into Th2 cells upon re‐stimulation.
Human IgE mediates stimulus secretion coupling in rat basophilic leukemia cells transfected with the α chain of the human high‐affinity receptor
Authors: Wilson A. Penelope M. , Pullar Christine E. , Camp Andrew M. , Helm Birgit A. 
Published: March 2007

AbstractCell surface expression of the a chain of the human (h) Fee receptor type 1 (FceR1) can be observed following stable transfection of RBL‐2H3 cells with the ha chain of the FceR1 complex. Association and dissociation constants for hIgE are similar to those previously reported for the ligand and its receptor. The demonstration of mediator release following the cross‐linking of hFcϵR1α by hIgE and antigen or anti‐hFcϵR1α antibody suggests that this system will assist the identification of structural motifs and specific amino acids that are involved in the generation of the signal(s) that will initiate and/or propagate the secretion of mediators from mast cells and basophils.
The involvement of CD14 in stimulation of cytokine production by uronic acid polymers
Authors: Espevik Terje , Otterlei Mark , Skjåk‐Braek Gudmund , Ryan Liv , Wright Samuel D. , Sundan Anders 
Published: March 2007

AbstractIn this study the molecular mechanisms behind the stimulatory activities of the uronic acid polymers poly mannuronic acid (poly M), high M alginate and oxidized cellulose (C60XY) were investigated and compared with lipopolysaccharide (LPS). The cytokine‐inducing abilities of the uronic acid polymers and LPS were examined on CD14‐positive human monocytes and CD14‐negative U373 astrocytoma cells. It was found that LPS induced monocytes and U373 cells to produce tumor necrosis factor (TNF) and interleukin(IL)‐6, respectively, by different mechanisms. The poly uronic acids induced monocytes to produce TNF, but with 100‐1000 times less potency compared to LPS. On U373 cells, LPS at concentrations ? 32 ng/ml resulted in a dose‐related IL‐6 production, whereas the poly uronic acids had negligible effects even at 1 mg/ml. The binding data demonstrate that only the CD14‐positive monocytes in the peripheral blood mononuclear cells population bound poly M. Furthermore, poly M was found to bind to CD14 in the presence of serum. Antibodies against CD14 also inhibited the TNF‐inducing activity of the three uronic acid polymers tested. In conclusion, these results demonstrate that uronic acid polymers induce TNF production through mechanisms which involve CD 14.
Neutrophil attractant/activation protein‐1 (interleukin‐8) induces in vitro neutrophil migration by haptotactic mechanism
Authors: Rot Antal 
Published: March 2007

AbstractThe role of leukocyte migration induced by the substrate‐bound attractants is obscured by the inability of standard methods for the study of leukocyte migration to dissociate chemotaxis and haptotaxis, migration in response to soluble and surface‐bound gradients of attractants. Here we show that the gradient of neutrophil attractant/activation protein‐1 (interleukin‐8, NAP‐1/ IL‐8) induces directed in vitro neutrophil migration when bound to the polycarbonate filter. In addition, we suggest that haptotaxis is responsible for neutrophil migration induced by NAP‐l/IL‐8 in standard Boyden‐type chemotaxis assays and, in light of the ability of NAP‐l/IL‐8 to bind to the endothelial cell surface and the extracellular matrix, could also be of great significance in vivo.
Differential cytokine expression in acute and chronic murine graft‐versus‐host‐disease
Authors: Allen Ruth D. , Staley Tabitha A. , Sidman Charles L. 
Published: March 2007

AbstractThe relationship between acute and chronic graft ‐versus‐host disease (GVHD) is not well understood. While both syndromes appear to result from recognition of host antigens by donor T cells, their pathological changes differ markedly. In light of the recent concept that helper T cells (Th) may be divided into two types based on their cytokine secretion profile and their ability to mediate cellular (Th1) or humoral (Th2) immunity, and considering the inflammatory nature of acute GVHD and the occurrence of significant B cell activation in chronic GVHD, we hypothesized that acute and chronic GVHD may be associated with differential cytokine production by activated T cells. To evaluate this hypothesis, we assessed expression of a range of cytokines in (C57BL/6 × DBA/2 )F1 (B6D2F1) recipients of C57BL/6 (acute GVHD), DBA/2 (chronic GVHD) or B6D2F1 (control) spleen cells. The results reported here indicate that a wide range of cytokines, including interleukin (IL)‐4, IL‐10, interferon‐γ, tumor necrosis factor β and macrophage inflammatory protein‐1α, are indeed differentially expressed in acute and chronic GVHD and support the concept that the pathology peculiar to acute or chronic GVHD may arise due to differential cytokine expression by activated Tcells.
Cross‐reactivity among evolutionarily distant major histocompatibility complex class I molecules (HLA‐B27 and H‐2Kk) revealed by xenoreactive T lymphocytes
Authors: Frangoulis Bernard , Reboul Murielle , Rocca Anna , Pla Marika 
Published: March 2007

AbstractA set of mouse HLA‐B27‐reactive cytotoxic T lymphocyte clones were found to recognize the HLA‐B27 molecule in an H‐2‐unrestricted manner, i.e. independently of any mouse major histocompatibility complex (MHC) molecule. The reactivity patterns of these clones on HLA‐B27 variants (positive only on HLA‐B*2702 and HLA‐B*2701) allowed the identification of residues N77 and A81 of the HLA‐B27 molecule as important for their reactivity. The location of these residues in the peptide‐binding groove (specificity pocket F) suggested that the reactivity of the clones is dependent on HLA‐B27‐bound peptide(s). However, several other class I molecules sharing these residues (N77 and A81) were not recognized, indicating that other residues might also be involved. One of the clones was found to display an interesting cross‐reactivity with allogeneic H‐2Kk molecules, sharing N77 and A81 with HLA‐B*2702. Sequence comparison suggested the involvement of residue H9, located in specificity pocket B of the peptide‐binding groove, and revealed some similarity of pockets B in HLA‐B27 and H‐2Kk. The structural basis of such T cell‐mediated MHC cross‐reactions across species barriers is discussed.
Selective engraftment of memory CD4+ T cells with an unusual recirculation pattern and a diverse T cell receptor‐Vβ repertoire into scid mice
Authors: Reimann Jörg , Rudoiphi Angelika , Tscherning Thomas , Claesson Mogens H. 
Published: March 2007

AbstractYoung (H‐2d, Ld+) severe combined immunodeficiency (scid) mice were injected intravenously with 105 CD4+CD8− T cells purified from spleen, thymus or lymph nodes (LN) of dm2 (H‐2d, Ld ) donor mice. In the immunodeficient recipients, the lymphoid compartment in the splenic white pulp was repopulated with donor‐type T cells and cellularity in the red pulp was increased. In addition, donor‐type CD4+ T cells repopulated the peritoneal cavity, mesenteric LN and the lamina propria of the small intestine of scid mice, but were undetectable in thymus and peripheral (inguinal, axillary) LN. Histological examination of repopulated mesenteric LN showed expanded subcapsular sinuses, repopulated cortical areas, but poorly developed high endothelial venules (HEV) indicating deficient blood‐LN lymphocyte recirculation. The engrafted CD4+ T cell population had the surface phenotype of memory T cells (CD44/Pgp‐lhigh CD45RBlow) and expressed the Peyer's patch HEV‐specific homing receptor CD49d (LPAM‐1), but not the LN HEV‐specific homing receptor LECAM‐l. The CD4+ T cell population in spleen and mesenteric LN of transplanted scid mice displayed a diverse T cell receptor‐V(3 repertoire. Transfer of titrated numbers (103, 104, 105 cells per mouse) of CD4+ T cells into scid mice established donor‐type T cell populations with this unusual homing pattern in all recipients. Repeated serial transfers of dm2 CD4+ T cells through young scid mice revealed an extensive in vivo expansion potential of transferred cells for > 18 months. The experimental system described represents an in vivo model to study the functional competence and the differentiation potential of a murine memory CD4+ T cell subset.
A human myeloma IgA with a hybrid heavy chain resulting from putative somatic gene conversion
Authors: Silvain Christine , Aucouturier Pierre , Leduc Isabelle , Mihaesco Edith , Homme Jean‐Louis Preud' , Cogné Michel 
Published: March 2007

AbstractA human monoclonal IgA1‐IgA2λ. hybrid molecule was detected in a myeloma patient homozygous for the A2m(1) allotype during a systematic study of monoclonal IgA with subclass‐specific monoclonal antibodies (mAb) and the lectin jacalin. This monoclonal immunoglobulin (GAU) reacted with both, although not with all, anti‐α1 and anti‐α2 mAb. Its heavy (H) chain contained an al hinge region as shown by jacalin reactivity, the presence of disulfide‐linked H and light chains in spite of its belonging to the IgA2m(1) allotype and amino acid composition of the isolated hinge region. The complete sequence of the H chain was deduced from that of complementary DNA clones from bone marrow cells. The CHI domain, hinge region and beginning of the CH2 domain and the membrane peptide were encoded by the al gene, with an insertion of an α2m(1) gene sequence accounting for the end of the CH2 and part or all of the CH3 domain (sequence identity between the two normal genes precludes a precise definition of breakpoints). The region of the 5′ recombination site included a repeat of a six base pair sequence which might play a role in the genetic exchange. The GAU hybrid a gene was undetectable in the patient's genomic DNA from polymorphonuclear cells. The genetic event which occurred at the level of the proliferating plasma cell clone is most likely to be a gene conversion.
Cross‐reactions of anti‐DNA autoantibodies with cell surface proteins
Authors: Raz Eyal , Ben‐Bassat Hanna , Davidi Talia , Shlomai Zipora , Eilat Dan 
Published: March 2007

AbstractAnti‐DNA autoantibodies are thought to play a major role in the pathogenesis of systemic lupus erythematosus. However, the mechanism(s) by which they participate in tissue and organ damage is not well understood. It has been suggested that these antibodies combine with DNA or DNA‐histone complexes to produce circulating immune complexes which may deposit in various tissues. Alternatively, anti‐DNA autoantibodies could interact directly with tissue components by way of immunological cross‐reaction.In this study we have used a panel of mouse monoclonal autoantibodies with anti‐nuclear specificity and measured their binding to membrane proteins of several tissues and cell lines. We show that the anti‐DNA antibodies, but not anti‐RNA or anti‐histone antibodies bind to membrane proteins of molecular weights 102,80,42,35 and 31 kDa, which are expressed in different combinations on several cell types. The binding of anti‐DNA antibodies to these cell surface proteins was not affected by DNase treatment of the target cells, was increased by DNase treatment of the antibody preparations and was completely inhibited by DNA, indicating a true cross‐reaction and not an indirect interaction of antibody and membrane proteins through a DNA bridge.Our results suggest that direct binding of anti‐DNA autoantibodies to cell surface membrane proteins may play an important role in the induction of the pleomorphic tissue damage in systemic lupus erythematosus.