bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of the gene linked to the T cell receptor β chain gene complex of NZW mice to the autoimmunity of (NZB × NZW)F1 mice
Authors: Hirose Sachiko , Tokushige Katsutoshi , Kinoshita Kohji , Nozawa Shingo , Saito Juichi , Nishimura Hiroyuki , Shirai Toshikazu 
Published: March 2007

AbstractWe have investigated the contribution to the autoimmune disease of (NZB × NZW)F1 (NZB/W) mice made by the T cell receptor β (TcR β) chain gene complex, or genes linked to it, that are derived from the NZW strain. For this, we developed the NZW.TcR βNZB strain, a NZW congenic line carrying the TcR β of NZB type, and produced NZB × NZW.TcR βNZB (NZB/W.TcR βNZB)F1 mice. We compared the amounts of anti‐DNA and anti‐histone antibodies and also the severity of lupus nephritis in these mice with those in the original NZB/W F1 mice. We obtained evidence for significantly lower serum levels of autoantibodies to double‐stranded and single‐stranded DNA and histone, and a later onset and a lower incidence of proteinuria in the NZB/W.TcR βNZB F1 mice than in the original NZB/W F1 mice. These findings clearly indicate that the gene (s) within or closely linked to the TcR β chain gene complex on chromosome 6 of the NZW strain acts to intensify the feature of systemic lupus erythematosus in the NZB/W F1 strain. The significant relationship of this finding to the strict dependency of NZB/W F1 disease on the H2d/H2z heterozygosity is discussed.
Activation of a natural killer clone upon target cell binding via CD2
Authors: Nakamura Tetsuya , Takahashi Kazuhisa , Koyanagi Makoto , Yagita Hideo , Okumura Ko 
Published: March 2007

AbstractThe functional relevance of CD2‐mediated signal transduction in triggering T cell receptor/CD3‐independent natural killer cell cytotoxicity was investigated by introducing wild‐type CD2 or signaling‐deficient CD2 with truncated cytoplasmic region into a murine natural killer‐like large granular lymphocyte clone lacking CD2 and T cell receptor/CD3. The introduction of wild‐type CD2 led to CD2‐dependent binding and cytotoxicity against P815 target cells. In contrast, the introduction of mutant CD2 with truncated cytoplasmic region led to comparable P815 binding but reduced cytotoxicity as compared with the wild type. These results provide a direct evidence for CD2‐mediated triggering of NK cell cytotoxicity upon target cell binding.
Transfection of human CD59 complementary DNA into rat cells confers resistance to human complement
Authors: Walsh Louise A. , Tone Masahide , Waldmann Herman 
Published: March 2007

AbstractWe have examined the role of the human CD59 antigen in inhibiting complement‐mediated lysis by transfer and expression of a CD59 cDNA in rat cells. A cDNA encoding CD59 was subcloned into the expression vector pSFSVneo and stably transfected into the rat T cell line NB2‐6TG. Indirect immunofluorescence staining using the anti‐CD59 monoclonal antibody YTH53.1 demonstrated the presence of human CD59 antigen on transfected cells and its attachment to the cell surface by a rat glycolipid anchor. Transfected cells were found to contain a single 3.3‐kb species of CD59 mRNA by Northern blot hybridization. Immunoblotting revealed that this encoded a protein band of the same size as that observed in human erythrocytes. To determine the biological effect of expression of human CD59 in rat cells, an assay was devised which measured the relative lysis of transfected cells compared to untransfected cells in the presence of human complement and a lytic monoclonal antibody. It was observed that CD59‐transfected rat cells are less susceptible to lysis by human complement and that this effect was blocked by a F(ab')2 fragment of YTH53.1. These experiments provide a direct demonstration that CD59 can function as an homologous complement restriction factor for nucleated cells.
Molecular mechanisms underlying lymphocyte recirculation II. Differential regulation of LFA‐1 in the interaction between lymphocytes and high endothelial cells
Authors: Tamatani Takuya , Kotani Masaharu , Tanaka Toshiyuki , Miyasaka Massayuki 
Published: March 2007

AbstractAlthough it has been suggested that LFA‐1 is one of the important molecules mediating interaction between lymphocytes and high endothelial (HE) cells, the implication was based on the observation that lymphocyte binding to high endothelial venules in frozen lymph node sections was partially inhibited by anti‐LFA‐1 monoclonal antibody at 4°. However, it has previously been unequivocally demonstrated that LFA‐1 molecule is unable to function at this low temperature.To assess the actual involvement of LFA‐1 in lymphocyte‐HE cell interaction at body temperature, we examined effects of newly developed anti‐rat LFA‐1 and anti‐rat ICAM‐1 monoclonal antibody on binding of resting or activated lymphocytes to a rat HE cell line at 37°. We found that (a) LFA‐1/ICAM‐1‐independent pathway was predominant in the interaction between resting lymphocytes and HE cells, indicating that LFA‐1 functions little, if any, in the interaction and (b) lymphocyte triggering through CD3 significantly increased binding inducing a LFA‐1/ICAM‐1‐dependent pathway, whereas phorbol 12‐myristate 13‐acetate stimulation also enhanced lymphocyte binding but inducing a LFA‐1‐dependent/ICAM‐1‐independent pathway. In both cases no apparent alteration in LFA‐1 expression was observed, suggesting that the increase in lymphocyte adhesion was not due to a quantitative but a qualitative change induced in LFA‐1 molecule upon lymphocyte stimulation. These findings suggest that LFA‐1 is normally inert but can be “switched” upon lymphocyte stimulation to participate in lymphocyte‐HE cell interaction, and that the LFA‐1's ligand specificity can be differentially regulated at the lymphocyte‐HE venule interface.
Regulation of LFA‐1‐mediated T cell adhesion by CD4
Authors: Mazerolles Fabienne , Hauss Pascale , Barbat Christiane , Figdor Carl. G. , Fischer Alain 
Published: March 2007

AbstractHeterotypic adhesion of T lymphocytes to monocytes. B lymphocytes, or other target cells is mainly mediated by LFA‐1 and CD2 molecules. Low‐affinity binding of resting T cells can be transiently up‐regulated by cross‐linking of CD3. We have previously found that binding of specific ligands to CD4 can down‐regulate adhesion of resting T cells to B cells. We now show that the enhanced adhesiveness of CD4+ T cells induced by CD3 cross‐linking using plastic‐bound anti‐CD3 antibody can also be inhibited by several CD4 ligands, i.e. anti‐CD4 antibodies, the gp160 env protein of human immunodeficiency virus, as well as by putative CD4 ligands, i.e. synthetic peptides analogous to the gp160‐binding site to CD4 (positions 418–434 and 449‐464) and a 12‐mer synthetic peptide (DR‐12) analogous to positions 35–46 of HLA class II β subunit and including the highly conserved Arg‐Phe‐Asp‐Ser (RFDS) sequence.After CD3 cross‐linking, maximal binding of T cells to HLA class II‐positive and ‐negative B cells was similar, although binding to HLA class II‐negative B cells was more prolonged. T cells that were passively induced to up‐regulate adhesion by binding of a CD11a‐specific antibody, NKIL16, known to enhance LFA‐1‐dependent adhesiveness, were less sensitive to the inhibitory effect of the DR‐12 peptide, whereas the inhibitory effects of gp160 were preserved. The kinetics of adhesion of NKIL16‐pretreated T cells was not influenced by HLA class II expression at the B cell surface. Together, these results strongly suggest that CD4‐HLA class II interaction may down‐regulate low‐affinity adhesion of resting T cells and, to some extent, high‐affinity adhesion of T cells actively induced by CD3 cross‐linking but not passively induced by an anti‐CD11a antibody.
Interleukio 2 stimulates serine phosphorylation of CD45 in CTLL‐2.4 cells
Authors: Valentine Mary A. , Widmer Michael B. , Ledbetter Jeffrey A. , Pinault Fran , Voice Robert , Clark Edward A. , Gallis Byron , Brautigan David L. 
Published: March 2007

AbstractLigation of interleukin 2 (IL2) is known to regulate both protein tyrosine and serine/threonine phosphorylation. A family of leukocyte transmembrane proteins whose cytoplasmic domain exhibits intrinsic protein tyrosine phosphatase activity is collectively called CD45 and is identified by a set of common cell surface epitopes. Although CD45 is known to be a phosphoprotein, it is not known how phosphorylation specifically regulates its function. We therefore identified a cell line, the IL 4‐dependent line CTLL‐2.4, in which CD45 could be phosphorylated in response to addition of IL 2. These cells are a variant of an IL 2‐dependent murine cell line which were selected for long‐term growth on IL 4 but which retain the ability to proliferate on exposure to IL 2. Incubation of CTLL‐2.4 in low serum concentrations followed by stimulation with IL 2 caused a three‐ to fivefold increase in the phosphorylation of CD45 in a time‐ and concentration‐dependent manner. CD45 in non‐stimulated cells contained one major tryptic phosphopeptide, whereas, after exposure of the cells to IL 2, two new phosphopeptides were present in CD45. The pattern of IL 2‐induced phosphorylation was different from that found following addition of phorbol 12‐myristate 13‐acetate (PMA) to the cells. Although IL 2 induced rapid and potent tyrosine phosphorylation in CTLL‐2.4 cells, all of the basal and cytokine‐activated phosphorylation of CD45 occurred on serine residues. The IL 2‐stimulated phosphorylation caused no change in the amount of cell surface CD45 and no alteration of its catalytic activity using an artificial tyrosine phosphorylated substrate‐RCM‐lysozyme. We speculate that the increase in phosphorylation of CD45 may modify its association with potential substrates. The differences in the phosphorylation patterns induced by IL 2 and PMA further suggest that more than one kinase can use CD45 as substrate and that IL2 activates a protein serine/threonine kinase different from protein kinase C.
Targeting behavior of rat monoclonal IgG antibodies in vivo: role of antibody isotype, specificity and the target cell antigen density
Authors: Yousaf Nasim , Howard Jonathan C. , Williams Bryan D. 
Published: March 2007

AbstractThe studies described in this report were designed to investigate factors that could influence the behavior of erythrocytes following their interaction with monoclonal antibodies (mAb) in a fully homologous experimental opsonization system in vivo. The clearance profiles and tissue distribution of target erythrocytes were examined in both normal and decomplemented rats preinjected with rat IgG2a or IgG2b mAb directed against the same or different sites on RT1Aa, the classical class I major histocompatibility complex antigen of the DA rat. Complement played a major role in augmenting the clearance and promoting hepatic sequestration of target erythrocytes in rats preinjected with IgG2a mAb directed against the S site. In contrast, an intact complement system was not an essential requirement for erythrocyte clearance when S site‐specific IgG2b mAb were used. With each antibody tested, (DA × PVG)F1 cells, expressing about half as much antigen, were removed significantly slower than DA erythrocytes, this finding being more pronounced when the animals had been preinjected with mAb of the IgG2a isotype. A comparison of the tissue distribution of DA and (DA × PVG)F1 erythrocytes indicated that hepatic uptake was greater for target cells expressing higher antigen density. A considerable degree of heterogeneity was observed in the in vivo behavior of the target erythrocytes with three groups of IgG2b mAb that recognized different sites on the class I molecule. The S site‐specific IgG2b mAb were much more efficient in the hepatic Fc receptor‐mediated clearance system than were the P site‐directed mAb of the same subclass. Our results suggest that antibody specificity may also be a contributory factor, in addition to antibody isotype and target cell antigen density, in determining the fate of target cells in vivo.
Correlation between the occurrence of lupus nephritis, anti‐erythrocyte autoantibodies and Vx haplotype in NZB × 129/J and NZB × SM/J recombinant inbred murine strains
Authors: Bailey Naila C. , Bona Alexandra , Dikman Steven , Bonilla Francisco , Alt Frederick W. , Bona Constantin 
Published: March 2007

AbstractThe NZB mouse is genetically predisposed to the development of autoimmune disease that resembles the human autoimmune systemic lupus erythematosus and autoimmune hemolytic anemia, with increased titers of anti‐DNA, and Coombs' autoantibodies. The various autoimmune traits are controlled separately by a limited number of genes. Genetic studies have shown that several immune loci are involved in autoimmunity: T cell abnormalities, H‐2 complex and immunoglobulin genes have been implicated. In this report, we present evidence for a significant correlation of NZB Vχ1 haplotype defined by restriction fragment length polymorphism analysis with anti‐erythrocyte autoantibodies in NZB × 129/J and NZB × SM/J recombinant inbred lines.
CD45R CD4 T cell subset‐reconstituted nude rats: subset‐dependent survival of recipients and bi‐directional isoform switching
Authors: Sparshott Sheila M. , Bell Eric B. , Sarawar Sally R. 
Published: March 2007

AbstractHigh and low molecular weight variants (CD45R) of the leukocyte common antigen (CD45) divide CD4 T helper cells into subpopulations which display distinct characteristics. In vitro and in vivo evidence suggested that the presence of the high molecular weight splice variants CD45RA or CD45RB distinguished naive CD4 T cells from memory T cells which underwent an irreversible switch to the low molecular weight isoform as a consequence of antigen encounter. In the rat monoclonal antibody MRC OX22 identifies an epitope on the CD45RB molecule. We investigated this proposed differentiation pathway by reconstituting athymic nude rats with highly purified OX22+ or OX22− CD4 T lymphocyte subsets obtained from the thoracic duct (TDL) of euthymic, congenic, allotype‐marked donors. Injection of CD4+CD45RB− (45R−) cells ensured long‐term survival of nude recipients; recipients of CD4+CD45R+ (45R+) cells died within 2–3 months of injection. Early after transfer (3–4 weeks) the progeny of both 45R+ and 45R− TDL were uniformly 45R−. With time (by 2 months) progeny of both parental types expressed the high molecular weight CD45RB isoform. Nude recipients of 45R− TDL always generated progeny a proportion of which bore the 45R+ phenotype; 3 months to 2 years post‐injection, 30%–50% of the donor‐derived CD4 T cells were 45R+. 45R− progeny isolated from primary recipients of either 45R− or 45R+ cells transferred into secondary nude recipients induced skin allograft rejection with equal effectiveness and also generated 45R+ offspring. The results indicated that CD4 T cell subsets switched between CD45R isoforms and that the change between high and low molecular weight expression was bi‐directional. The splice variants apparently are not lineage or maturation markers, but rather identify CD4 T cells that exist transiently in different functional states.
Differential reactivity of Vβ9 T cells to minor lymphocyte stimulating antigen in vitro and in vivo
Authors: Utsunomiya Yasunori , Kosaka Hiroshi , Kanagawa Osami 
Published: March 2007

AbstractThe monoclonal antibody (mAb) MR10‐2 is specific for mouse T cells expressing the Vβ9 chain of T cell antigen receptor. This mAb reacts with 2% of peripheral T cells in a number of different strains of mice, but in mice expressing the minor lymphocyte stimulating (Mls)‐1a antigen, Vβ9+ T cells recognized by MR10‐2 are deleted. However, we failed to demonstrate the Mls‐1a antigen‐specific response of naive, non‐activated Vβ9 T cells in vitro. On the other hand, T cells activated initially with anti‐Vβ9 (MR10‐2) mAb in vitro are capable of responding to the Mls‐1a antigen. These results demonstrate that Mls‐1a reactivity of Vβ9 T cells depends on the activation state of the T cells, suggesting a differential activation requirement between naive, non‐activated T cells and previously activated T cells.
Functional importance of CD4+ and CD8+ cells in cytotoxic lymphocytes activity and associated gene expression. Impact on the age‐related decline in lytic activity
Authors: Bloom Eda T. 
Published: March 2007

AbstractPreviously we found that the age‐related decline in cytotoxic lymphocyte (CTL) activity in a murine allogeneic system is associated with declining expression of the perforin and two serine esterase genes by senescent CTL. To identify the cell subsets responsible for the age‐related decrement in the generation of CTL, splenic T cells, subsets, and mixtures of subsets from aging and young BALB/c female mice were analyzed for their allo‐responsiveness to C57BL/6 spleen cells. Depletion studies revealed that CD8+ cells expressed both the lytic activity and the CTL‐associated genes, although both CD8+ and CD4+ cells were required for generation of optimal lytic and proliferative responses. Mixture experiments demonstrated that the reduced lytic activity generated by CD8+ cells from the spleens of old mice is a consequence of alterations in both CD8+ and CD4+ cells. The results of experiments in which CD4+ cells from young and old mice were mixed revealed that the alteration in CD4+ cells is consistent with a loss of function. These findings show that (a) the expression of the perforin and serine esterase genes in primary CTL is associated with CD8+ T cells in old and young mice, and exhibits an age‐related decrement consistent with that for lytic activity, and (b) the senescent decline in CTL activity is a consequence of aging decreasing activity in both the CD4+ and CD8+ subsets.
Independent regulation of 55‐kDa and 75‐kDa tumor necrosis factor receptors during activation of human peripheral blood B lymphocytes
Authors: Erikstein Bjørn K. , Smeland Erlend B. , Blomhoff Heidi Kiil , Funderud Steinar , Prydz Kristian , Lesslauer Werner , Espevik Terje 
Published: March 2007

AbstractWe have studied the expression of two different tumor necrosis factor receptors (TNFR; 55 kDa and 75 kDa) on resting and activated human peripheral blood B lymphocytes using specific monoclonal antibodies (mAb). Flow cytometric analysis revealed that most resting B cells expressed small amounts of the 75‐kDa TNFR, and that the 75‐kDa TNFR was markedly up‐regulated upon stimulation with anti‐μ or Staphylococcus aureus Cowan strain I (SAC). In contrast, the expression of the 55‐kDa TNFR was low on resting as well as on activated cells. B cell activation was accompanied by an increased binding of biotinylated TNF‐α, and this binding could be blocked by preincubation by utr‐1 (anti‐75‐kDa TNRF), but not the htr (anti‐55‐kDa TNFR) antibodies. Notably, a number of cytokines tested (interleukin 1 to 8, interferon‐γ, TNF‐α and ‐β) did not influence the expression of either the 75‐kDa or the 55‐kDa TNFR when given to resting B cells. Moreover, phorbol 12‐myristate 13‐acetate led to an early, marked down‐regulation of the 75‐kDa TNFR expression, followed by a later modest increase after > 24 h. In contrast to other cell systems where htr mAb have been found either to mimic or to inhibit TNF action, htr mAb had insignificant effects in assays for restimulation of preactivated B cells. However, utr‐1 markedly inhibited the TNF‐β but only partly inhibited the TNF‐α‐induced proliferation. Taken together, our data suggest that changes in 75‐kDa protein expression is responsible for the increased TNFR expression on activated vs. resting peripheral blood B cells and that this protein also may play an important functional role.
Characterization of the induction of persistence of major histocompatibility complex class II by hybrids of macrophages from Bacillus Calmette Guerin‐resistant mice
Authors: Faris Mary , Zwilling Bruce S. 
Published: March 2007

AbstractPeritoneal macrophages (MΦ) from mice that are resistant to infection by Mycobacterium bovis (strain BCG) (Bcgr) can be induced to express major histocompatibility complex (MHC) class II glycoproteins (I‐A) continuously upon treatment with 100 units of recombinant interferon‐γ (rIFN‐γ). In contrast, MΦ from mice that are susceptible to BCG (Bcgs) express I‐A transiently. Persistent expression of I‐A does not require the continued synthesis of the glycoprotein. Thus, treatment with cycloheximide (CHX) reduces I‐A expression by MΦ that express I‐A transiently but does not affect the expression of I‐A that is persistently expressed. It was not possible, in these studies, to characterize the induction of persistence independent of MHC class II expression because of the 24–48 h required for MHC class II synthesis and cycling to the cell surface. During this time, persistence was also induced. To characterize persistence independent of MHC class II induction we have produced MΦ‐MΦ somatic cell hybrids that express I‐A constitutively by fusing cells from a Bcgs MΦ cell line with MΦ from Bcgr mice. Treatment of some of the hybrids with CHX reduced MHC class II expression. The MΦ hybrids required treatment with high doses of rIFN‐γ to induce CHX‐resistant I‐A expression. The induction of the persistence of I‐A, following the addition of rIFN‐γ, required a short burst of protein synthesis as well as the presence of rIFN‐γ for at least 3 h. The addition of actinomycin D simultaneously with rIFN‐γ did not prevent the induction of the persistence of I‐A expression by one of the MΦ hybrids (F6.4). In contrast, the induction of persistence of I‐A expression required a longer period of induction than was observed for hybrid F6.4, which was attributed to the requirement for new RNA and protein synthesis by the A1.8 hybridoma.
A major fraction of human intraepithelial lymphocytes simultaneously expresses the γ/δ T cell receptor, the CD8 accessory molecule and preferentially uses the Vδ1 gene segment
Authors: Deusch Kai , Lüling Friedrich , Reich Kristian , Classen Meinhard , Wagner Hermann , Pfeffer Klaus 
Published: March 2007

AbstractThe frequency of T cell receptor (TcR) type and the variable gene segment expression in human intraepithelial lymphocytes (IEL) from the large intestinal mucosa were studied by flow cytometry and immunohistochemistry, and compared to those in peripheral blood lymphocytes (PBL) — or lamina propria lymphocytes (LPL). Employing anti‐γ/δ TcR and anti‐α/β TcR monoclonal antibodies (mAb), flow cytometric analysis revealed that a large fraction of IEL (37%) are γ/δ T cells, whereas within LPL and PBL γ/δ T cells comprise a minor population (4.6% and 3.8% respectively). At these sites the number of γ/δ T cells labeled with anti‐CD8 mAb were 58.3% (IEL), 43.3% (LPL) and 24.4% (PBL). In situ staining of serial sections of large intestine confirmed these results. Hence, these data suggest a selective accumulation of CD8+ γ/δ T cells in the human epithelium of the large intestine. Furthermore, analysis of γ/δ TcR bearing IEL+ disclosed a marked preponderance of cells using the Vδ1 gene segment, whereas γ/δ TcR+ PBL preferentially express Vδ2. Strikingly, the majority of these Vδ1+ IEL bear the CDS molecule on their surface. These results are taken as evidence for a selective localization of Vδ1+ CD8+ γ/δ T cells in the epithelium of the large instestine.