bluuebunny/crossref_metadata_2025_split huggingface dataset:
A peptide binding weakly to the major histocompatibility molecule augments T cell responses
Authors: Feng Ming‐Hsien Lin , Lai Ming‐Zong 
Published: March 2007

AbstractAn I‐Ad‐derived peptide PB1 was found to enhance the reactivity of I‐Ad‐restricted T cells. The augmentative effect was not due to the cross‐reactivity of PB1 peptide with antigens. PB1 had no effect on T cells specific for I‐Ab and I‐Ek, nor did PB1 increase the T cell responses to concanavalin A and staphyloccocal enterotoxin B. The strict I‐Ad specificity suggests that PB1 enhances the recognition of antigen‐I‐Ad complex by T cell receptor. PB1 bound to I‐Ad weakly. The augmentative effect could be found on other I‐Ad‐binding peptides in appropriate conditions; however, PB1 was distinct in its prominently augmentative effect on all the I‐Ad‐restricted T cells analyzed. A similar enhancing activity was demonstrated on a synthetic transferrin receptor peptide with minimum affinity for I‐Ad. The unusual enhancing activity of PB1 may thus be attributed to the low I‐Ad binding affinity. It was postulated that the binding of low‐affinity PB1 would not only stabilize I‐Ad structure, but also enhance the binding of other peptides. This was supported by the increased binding of OVA 323‐339 and cI 84–98 to I‐Ad in the presence of PB1. The inclusion of PB1 in the immunization mixture also enhanced T cell responses in vivo, suggesting the possibility of using low‐affinity peptide to promote specific immunity.
Human tonsil, blood and bone marrow in vivo‐induced B cells capable of spontaneous and high‐rate immunoglobulin secretion in vitro: Differences in the requirements for factors and for adherent and bone marrow stromal cells, as well as distinctive adhesion molecule expression
Authors: Brieva José A. , Roldán Ernesto , Rodríguez Carmen , Navas Gloria 
Published: March 2007

AbstractHuman B cells capable of spontaneous IgG secretion are commonly found in circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The present study compares the mechanisms that regulate tonsil, blood and BM B cells capable of spontaneous IgG secretion. The BM cell subset produced IgG during a markedly longer period of time (14 days) than did tonsil and blood cell subsets (2–3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the presence of adherent cells, as demonstrated by adherent cell depletion and re‐addition experiments. Stromal BM cells supported linear IgG secretion by non‐adherent BM cells for 2 weeks, but were unable to prolong the short‐term IgG secretion by tonsil and blood cells. Different factors induced IgG secretion in each of the three B cell populations as optimal IgG secretion by tonsil, blood or BM cell subsets required either tumor necrosis factor‐α, interleukin‐6 or fibronectin + interleukin‐6, respectively. Finally, these populations also showed differences in the expression of adhesion molecules; the tonsilar cell subset was PNA+/− CD44+ CD49d+ CD49e− Leu‐8+/−, the blood cell subset was PNA− CD44+/− CD49d+ CD49e− Leu‐8+ and the BM cell subset was PNA− CD44+/− CD49d+ CD49e− Leu‐8−. These results suggest that the mechanisms controlling the final differentiation and the expression of adhesion molecules in these B lymphocytes exhibit territorial specificity.
Profound reduction in allergen sensitivity following treatment with a novel allergy vaccine
Authors: Hellman Lars 
Published: March 2007

AbstractA novel approach is described for the treatment of IgE‐mediated allergic reactions which is based on the induction of a strong anti‐IgE response in the host. Vaccination of ovalbumin‐sensitized rats with constant domains two and three of rat IgE coupled to a heterologous carrier protein resulted in a profound decrease in serum levels of IgE, and later in a nearly complete block of histamine release from mast cells and basophils upon challenge with either a cross‐linking polyclonal anti‐IgE antiserum or a specific allergen.
A novel soluble form of mouse VCAM‐1 is generated from a glycolipid‐anchored splicing variant
Authors: Hahne Michael , Lenter Martin , Jäger Ute , Vestweber Dietmar 
Published: March 2007

AbstractVCAM‐1 is a cytokine‐induced endothelial adhesion molecule which belongs to the immunoglobulin (Ig) superfamily and mediates the binding of various leukocytes. In addition to the 110‐kDa form of VCAM‐1, we have found four additional glycoproteins on mouse brain‐derived endothelioma cells after stimulation with tumor necrosis factor‐α (TNF‐α), which are recognized by several monoclonal antibodies against VCAM‐1. Biochemical analysis revealed that the two smaller proteins (35 kDa and 37 kDa) are intracellular precursors of the two larger forms (44 kDa and 45 kDa), that the 44 kDa and 45 kDa proteins are glycolipid‐anchored at the cell surface and that they differ in their N‐glycosylation. Most likely they are identical to the recently identified glycolipid‐anchored splice variant of VCAM‐1, since they are recognized by the M3 antiserum which we raised against a peptide from the unique protein domain of this splicing variant. With the help of this antiserum we could show by immunohistology that the corresponding VCAM‐1 protein variant is induced in vivo by lipopolysaccharide (LPS) on endothelium of the mouse. In addition, we found a 42‐kDa soluble form of VCAM‐1 in the serum of LPS‐stimulated mice, which was recognized by the M3 antiserum. This soluble form was undetectable in the serum of unstimulated mice in contrast to the soluble 100‐kDa form of VCAM‐1 which was clearly detected in serum of unstimulated mice and only increased 2–3‐fold upon stimulation with LPS. Thus, only the expression of the 42‐kDa shedded form and not of the 100‐kDa soluble form of VCAM‐1 is strictly dependent on stimulation by LPS.
Differential effects of superantigen‐induced “anergy” on priming and effector stages of a T cell‐dependent antibody response
Authors: Lussow Alexander R. , MacDonald H. Robson 
Published: March 2007

AbstractThe in vitro T cell nonresponsiveness or anergy to restimulation with staphylococcal enterotoxin B (SEB) following the in vivo injection of the superantigen is well characterized. Here we use mice transgenic for a Vβ8.2+ T cell receptor (TcR) (reactive with SEB) to establish a large population of anergic T cells in vivo. As expected, peripheral T cells from the SEB injected transgenic mice failed to proliferate or produce interleukin (IL)‐2 following restimulation with the superantigen in vitro. However, in this system superantigen reactivity could be restored by either addition of exogenous IL‐2, or stimulation with immobilized anti‐TcR antibody. To evaluate the effects of superantigen‐induced anergy in vivo, SEB‐injected or noninjected control transgenic mice were immunized and boosted with the T cell‐dependent antigen tetanus toxin (TT). SEB injection of the Vβ8.2+ transgenic mice 5 days prior to the TT immunization inhibited the anti‐TT antibody response as measured over a 100‐day period, whereas injection of a superantigen which does not interact with the Vβ8.2+ TcR (such as SEA) did not. Furthermore, SEB injection of control nontransgenic mice did not interfere with the induction of a high titer anti‐TT antibody response. In contrast to the inhibition seen when SEB was given prior to TT immunization, injection of transgenics with SEB either after the priming TT immunization or after the recall booster injection did not significantly influence the titers of anti‐TT antibodies produced. These results demonstrate that the establishment of peripheral T cell anergy to superantigens inhibits the specific antigenic priming of helper T cells in vivo, but does not prevent primed T cells from helping B cells to mount an effective antibody response.
B‐T cell interactions modulate inhibitory effects of interleukin‐4 on human B cell proliferation
Authors: Taieb Joelle , Auffredou Marie‐Thérese , Vazquez Aimé 
Published: March 2007

AbstractIn this study, we investigated the role of B‐T cell contacts in interleukin Ia‐mediated inhibition of human B lymphocyte proliferation induced by mitogenic doses of soluble anti‐μ monoclonal antibody (mAb). We show that additional cross‐linking of B cell antigens, using Sepharose beads coated with anti‐μ, anti‐(IL)‐4 mAb (but not soluble mAb) or anti‐CD40 antigen counteracted the inhibitory activity of IL‐4. More importantly, cell contacts between B cells and activated T cells (but not unstimulated T cells) were sufficient to counteract IL‐4‐mediated inhibition of DNA synthesis. In addition, the inhibitory activity of IL‐4 on chronic lymphocytic leukemia B cells stimulated with anti‐μ and IL‐2 was itself reduced by the presence of fixed activated T cells. Our data suggest that a major role for IL‐4 would be to prepare B cells to receive additional mitogenic signals through cell contact interactions with activated T lymphocytes. When such interactions do not occur IL‐4 may block DNA synthesis, preventing uncontrolled B cell proliferation.
CD8+ cytolytic T lymphocytes become infected in vitro in the process of killing HIV‐1‐infected target cells
Authors: De Maria Andrea , Colombini Sandra , Schnittman Steven M. , Moretta Lorenzo 
Published: March 2007

AbstractIn the present study the requirements for in vitro infection of antigen‐specific CD8+ cytotoxic T lymphocytes (CTL) with human immunodeficiency virus –1(HIV‐1) were investigated. CD3+CD8+CD4− HIV‐1 nef‐specific CTL become infected with HIV‐1 after short‐term co‐culture with HLA‐matched HIV‐1‐infected CD20+ B lymphoblastoid cells (B‐LCL) which are specifically killed. Similar results were observed with an allospecific CD8+ CTL population. In addition, co‐culture experiments showed that once infected with HIV‐1, these CD8+ CTL could spread the infection further to uninfected CD4+ lymphocytes. In contrast, CD8+ CTL did not become infected with HIV‐1 when co‐cultured with HLA‐mismatched HIV‐1‐infected B‐LCL which are not killed.These observations in vitro could have relevance in peripheral lymphoid organs contributing to the progressive decrease of HIV‐specific CD8+ CTL activity that is associated with the progression to AIDS.
MRC OX19 recognizes the rat CD5 surface glycoprotein, but does not provide evidence for a population of CD5bright B cells
Authors: Vermeer Lilian A. , De Boer Nynke K. , Bucci Cecilia , Bos Nico A. , Kroese Frans G. M. , Alberti Saverio 
Published: March 2007

AbstractTo clone the rat CD5 gene we first produced two rat CD5 probes. The probes were obtained by polymerase chain reaction (PCR) on rat genomic DNA using primers designed on conserved regions between mouse and human CD5. The screening of a rat cDNA library at high stringency using these probes resulted in a 1.5‐kb positive clone. The DNA sequence of this clone confirmed its CD5 nature, but the clone appeared to lack part of the 5′ and part of the 3′ end. These missing 5′ and 3′ ends were obtained by PCR on rat thymus RNA. By ligating these PCR products to the original 1.5‐kb CDM8 clone, a full‐length rat CD5 gene was constructed. The full‐length clone showed high identity with mouse and human CD5; however, at the 5′ site of the gene a region of 36 nucleotides is present which is not seen in either mouse or human CD5. We have evidence that this sequence is a normal constituent of the rat CD5 gene: first, it is in frame with the rest of the CD5 coding sequence; second, it does not contain a stop codon; and third, it is also present in the CD5 gene of other rat strains. We transfected the full‐length CD5 construct in COS cells and demonstrated that indeed the CD5 protein is recognized by MRC OX19. Although we showed that CD5 mRNA is present in rat B cells, extensive flow cytometry analysis using MRC OX19 as antibody failed to detect B cells expressing significant levels of CD5 on their cell surface compared to other B cells in any tissue or cell suspension tested from a variety of rat strains. This is in contrast with the mouse where a distinct population of B cells (B‐la cells) can be found expressing more CD5 than the other B cells. Either B‐1 cells are not present in rats or CD5 is not the right phenotypic marker for rat B‐1 cells. It still remains to be investigated whether a population of B cells with functions similar to those of murine B‐1 cells is present in rats.
Targeted neutralization of the complement membrane attack complex inhibitor CD59 on the surface of human melanoma cells
Authors: Junnikkala Sami , Hakulinen Juha , Meri Seppo 
Published: March 2007

AbstractMajor problems in the immunotherapy of human tumors with complement‐activating monoclonal antibodies (mAb) are (i) inherent resistance of tumor cells to complement cytolysis and (ii) a possible undiscriminatory attack against normal cells. In the present study we have developed a procedure to simultaneously direct the complement membrane attack complex and neutralize its inhibitor CD59 (protectin) on human melanoma cells in vitro. G361 melanoma cells were selectively recognized in heterogenous cell mixtures by a complement‐fixing mAb (R24) against the tumor cell GD3‐ganglioside. Biotinylated anti‐CD59 mAb (YTH53.1) was directed to the tumor cells with a high‐affinity biotin‐avidin bridge using a proportion of R24 as a biotinylated targeting mAb and avidin as a linker. Biotinylated anti‐CD59 mAb lost its ability to activate complement, but retained its CD59‐neutralizing activity. Thus, it was possible to avoid nonspecific lysis of surrounding erythrocytes and endothelial cells and direct the CD59‐neutralizing effect to the tumor cells. As a result the tumor cells were efficiently killed by R24 plus complement while the bystander cells remained viable. These results suggest that it is possible to target an unrestricted complement membrane attack against GD3‐ and CD59‐positive melanoma cells.
Early degenerate selection of thymocytes by class I major histocompatibility complex
Authors: Grassi Fabio , Barbier Eliane , Cazenave Pierre‐André 
Published: March 2007

AbstractOntogeny of T cells is accomplished in the thymus by a process of positive selection, in which interaction of the T cell receptor (TcR) expressed on CD4+8+ thymocytes with self major histocompatibility complex (MHC), expressed on cortical epithelial cells, determines the progress along the maturation pathway and confers self restriction to T cells. Conversely, cells behaving as self reactive by interaction with bone marrow‐derived antigen‐presenting cells are negatively selected by apoptosis. We show here that the presence of a class I‐restricted soluble TcR (sTcR) in the fetal thymic microenvironment, early in T cell ontogeny, determines an enhanced negative selection of a sizeable number of CD4+8+ thymocytes, which have been previously subjected to a positive‐selection event. We hypothesize that the generation of the mature thymic T cell repertoire stems from an interaction of TcR, under a critical affinity threshold, with a self peptide‐MHC complex which is common to a great number of TcR specificities using the same restriction element. A shift in this affinity threshold, caused by sTcR, results in the generation of cells acting in a self‐reactive manner, which are then deleted. In extended fetal thymus organ culture in the presence of sTcR, we have also observed the appearance of mature CD8+ T cells, which once adoptively transferred to syngeneic nude mice are expanded in the periphery, consistent with an enhanced avidity of these cells for self MHC.
Engagement of MHC class II molecules by staphylococcal superantigens activates src‐type protein tyrosine kinases
Authors: Morio Tomohiro , Geha Raif S. , Chatila Talal A. 
Published: March 2007

AbstractStaphylococcal exotoxins (SE) are superantigens that bind to monomorphic determinants on major histocompatibility complex (MHC) class II molecules and stimulate human peripheral blood T lymphocytes in a Vβ‐specific manner. SE also deliver activation signals via MHC class II molecules that initiate cell adhesion and cytokine gene transcription. These events are preceded by tyrosine phosphorylation and are antagonized by inhibitors of tyrosine kinases, indicating an essential role for these kinases in signaling via class II molecules. We report that stimulation of human peripheral blood monocytes with SE induced rapid and selective activation of the src‐related protein tyrosine kinases (PTK) fgr and hck. SE also induced the activation of fgr and lyn in B cells. PTK activation by SE required MHC class II expression, and was greatly potentiated in the presence of T cells bearing toxin‐specific Vβ chains. These results indicate that in addition to their antigen and superantigen‐presenting function, MHC class II molecules act as signal‐transducing receptors that are coupled to src‐type PTK.
Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major
Authors: Assreuy Jamil , Cunha Fernando Q. , Epperlein Monica , Noronha‐Dutra Alberto , O'Donnell Catherine A. , Liew Foo Y. , Moncada Salvador 
Published: March 2007

AbstractMurine macrophages can be activated to produce nitric oxide (NO) and superoxide and these two radicals can react to form peroxynitrite, a powerful oxidant which may be involved in parasite killing. We now show that murine macrophages activated with zymosan and interferon‐γ (ZYM/IFN‐γ) produced both superoxide (peaking 1–2 h after stimulation, then rapidly declining) and NO (barely detectable at 6 h, peaking by 24 h). Macrophages activated with ZYM alone produced only superoxide, while stimulation with lipopolysaccharide (LPS) and IFN‐γ induced NO but not superoxide. Cells stimulated with ZYM/IFN‐γ or LPS/IFN‐γ killed Leishmania major to a similar degree, an effect that was completely blocked by the addition of N‐iminoethyl‐L‐ornithine. However, macrophages stimulated with ZYM alone were unable to kill L. major. S‐nitroso‐acetyl‐penicillamine, which release NO, was highly leishmanicidal when added directly to the parasites. 3‐morpholino‐sydnonimine hydrochloride which releases both NO and superoxide simultaneously, was also efficient at killing L. major and this cytotoxicity was greatly enhanced by the addition of superoxide dismutase. Finally, authentic peroxynitrite failed to induce any cytotoxic effect, even at a high concentration. Thus macrophages can produce either NO, superoxide or both, depending on the stimulus. However, the killing of L. major is dependent only on the production of NO.
The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen
Authors: Latza Ute , Dürkop Horst , Schnittger Susanne , Ringeling John , Eitelbach Florian , Hummel Michael , Fonatsch Christa , Stein Harald 
Published: March 2007

AbstractTissue distribution and expression on mitogen and virally stimulated lymphocytes render the ACT35 molecule a human lymphocyte activation antigen which as yet could not be clustered. Expression cloning of the ACT35 antigen from a pCDM8 library of the HUT‐102 cell line revealed strong homology of the cDNA and its encoded protein sequence with the formerly described rat OX40 antigen. The 1.4‐kb nucleotide sequence and the deduced 277‐amino acid sequence of the single transmembrane protein were 65% and 63% identical, in human and in rat, respectively. Conservation included one N‐linked glycosylation site and one protein kinase C phosphorylation site. When expressed in COS‐1 cells, the cDNA presented properties comparable to the native ACT35 antigen and the rat OX40 molecule (relative molecular mass 48000). Thus, the ACT35 protein corresponds to the hitherto unknown human OX40 antigen and is, therefore, another member of the tumor necrosis factor/nerve growth factor receptor (TNFR/NGFR) family. After applying fluorescence in situ hybridization, the human ACT35/OX40 gene could be mapped to chromosome band 1p36 and is, thus, linked to the genes for TNFR II and CD30.
The effect of rapamycin on T cell development in mice
Authors: Luo Hongyu , Duguid William , Chen Huifang , Maheu Michel , Wu Jiangping 
Published: March 2007

AbstractRapamycin (RAPA) is a strong immunosuppressant with a chemical structure similar to that of FK506, although it acts by a mechanism different from both FK506 and cyclosporin A. The effect of RAPA on T cell development in mice was investigated in this study. RAPA caused significant thymic atrophy. The major histological change in the RAPA‐treated thymus was thinning of the cortex. No other apparent damage in the cortex or medulla was observed. Consistent with these histological findings, in vivo thymocyte cycling was blocked by RAPA before the S phase, and the ex vivo and in vitro proliferation of the thymocytes was also strongly repressed by the drug. According to electron microscopy and DNA fragmentation assays, RAPA did not induce apoptosis. These results indicate that the repressed thymocyte proliferation is a major mechanism causing RAPA‐induced thymic atrophy. Further, RAPA had no effect on thymocyte apoptosis induced by anti‐CD3 or ionomycin, and the drug did not interfere with deletion of CD4+8+ thymocytes or peripheral Vβ6+ T cells induced by anti‐CD3 or Mls‐1a, respectively. These data suggest that RAPA does not hamper the negative selection. There was a relative increase in the CD3− fraction of the de novo developing CD4 and CD8 double‐positive (DP) thymocytes in the RAPA‐treated mice. Moreover, there were relative increases of the CD3− fractions of the CD4 or CD8 single‐positive (SP) cells in both the thymi and periphery. The generation of the CD3− SP under the influence of RAPA could be used as a useful model for further study of the function and signal transduction of these CD3‐defective SP cells.
D‐penicillamine‐ and quinidine‐induced antinuclear antibodies in A.SW (H‐2s) mice: similarities with autoantibodies in spontaneous and heavy metal‐induced autoimmunity
Authors: Monestier Marc , Novick Kristine E. , Losman Michele J. 
Published: March 2007

AbstractTen percent of human lupus syndromes occur in patients as a result of treatment with certain medications. H‐2s mice can produce autoantibodies following treatment with various drugs or heavy metals and they are a potential animal model of drug‐induced lupus. We have examined nine anti‐chromatin monoclonal antibodies (mAb) from A.SW mice that had been treated with either D‐penicillamine or quinidine, two lupus‐inducing drugs in humans. These mAb are specific either for DNA or histone‐DNA complexes corresponding to nucleosomes or subnucleosome particles. Only one mAb reacts with an unknown chromatin antigen. The V region sequences of six of these mAb were studied and are notable by several features. As previously observed in spontaneous autoantibodies to DNA or histone‐DNA complexes, arginine or asparagine residues are found at critical locations throughout the V regions. Many of these residues, potentially important for binding to DNA or DNA‐histone complexes, result either from somatic mutations or atypical VH‐D‐JH rearrangements. Another significant characteristic is that the VH genes of several D‐penicillamine‐ or quinidine‐induced mAb are most similar to those of anti‐nucleolar mAb obtained from mercury‐injected A.SW mice. The implications of these findings for the pathogenesis of spontaneous or induced autoimmunity are discussed.