bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of rats with monoclonal anti‐CD4 induces long‐term resistance to streptococcal cell wall‐induced arthritis
Authors: Van Den Broek Maries F. , Van De Langerijt Lex G. M. , Van Bruggen Mieke C. J. , Billingham Mike E. J. , Van Den Berg Wim B. 
Published: March 2007

AbstractTo investigate the role of CD4+ cells in the induction and maintenance of streptococcal cell wall (SCW)‐induced arthritis, Lewis rats were treated with a monoclonal antibody against rat CD4 (W3/25). Injection before onset of the arthritis resulted in resistance to SCW arthritis. Treatment with anti‐CD4 during ongoing arthritis induced an amelioration of the arthritis, demonstrating that CD4+ cells are involved in both the induction and effector phases of the chronic arthritis.After return of CD4+ cells to normal levels in the circulation, no arthritis occurred in protected rats, despite the continued presence of SCW in the body. Even reinjection of SCW could not induce arthritis in these rats, suggesting that tolerance to SCW had occurred. In addition, these tolerized rats were refractory to actively induced adjuvant arthritis (AA), but were susceptible to passively transferred AA.Our data imply, that (a) treatment with anti‐CD4 plus SCW induces a long‐term resistance to SCW‐induced arthritis and adjuvant arthritis, (b) SCW and M. tuberculosis may use similar mechanisms of regulation of arthritis and (c) active peripheral suppression is not the mechanism of this nonresponsiveness.
Developmentally controlled selection of antibody genes: Characterization of individual VH7183 genes and evidence for stage‐specific somatic diversification
Authors: Carlsson Leif , Övermo Charlotta , Holmberg Dan 
Published: March 2007

AbstractNucleotide sequence analysis of a large number of rearranged immunoglobulin heavy chain V region genes allowed the identification of six new members of the VH7183 gene family. These six new genes plus the eight previously defined genes agrees with the previously estimated complexity of this gene family. Twelve of these genes were represented among the isolated clones. A comparison of the clones, derived from 1‐day‐ and 14‐week‐old BALB/c mice, suggested a biased and developmentally controlled VH7183 gene utilization.Furthermore, a developmentally controlled, non‐random distribution of the functional vs. non‐functional VHDJH rearrangements was observed among clones utilizing genes of this family, suggesting unsuspected regulatory aspects of Ig rearrangements in the process of B cell differentiation. Finally, a limited junctional diversity was revealed among the neonatal clones as the result of a low frequency of N‐sequence addition. A similar discrepancy was also observed between neonatal and adult VH1558 clones. In conclusion, these data suggest a programmed generation of B cell diversity similar to what has been observed for the establishment of γ/δ T cell repertoires.
Differential effect of interleukin 1 on naive and memory CD4+ T cells
Authors: Luqman Mohammad , Greenbaum Laurence , Lu Dandan , Bottomly Kim 
Published: March 2007

AbstractFreshly derived murine CD4+ T cells are divided into naive and memory cells based on the expression of CD45 isoforms. Cross‐linking the T cell receptor CD3 complex either by plastic‐bound anti‐CD3 antibodies or the antibody presented on non‐lymphoid Fcγ receptor type II‐positive Chinese hamster ovary cells in absence of competent antigen‐presenting cells fails to activate naive cells to either secrete cytokines or to proliferate. In contrast, memory cells secrete their characteristic cytokines [interleukin (IL) 2, IL4, and interferon‐γ] and show significant proliferation to this stimulus. IL 1 however, is required for their optimal clonal expansion. Differential expression of IL 1 receptor mRNA in memory cells also correlate with their responsiveness to IL 1. Thus, these data reveal a basic difference in the requirements for activation of naive and memory CD4+ T cells.
Latent help to and from H‐2 antigens
Authors: Mitchison Avrion 
Published: March 2007

AbstractAn optimized system for probing allo‐immunity to major histocompatibility complex (MHC) antigens by means of adoptive transfer is used to confirm and extend previous work showing that naturally occurring class I MHC antigens, while capable of inducing Th activity when presented in combination with other allo‐antigens, fail to do so on their own. The Th activity which they do induce develops slowly, after repeated immunizations, and can properly be described as “latent”. Latency, or “cripticity” as it is also termed, may help explain how autoimmune disease is initiated.
Restricted Vα2.3 gene usage by CD4+ T lymphocytes in bronchoalveolar lavage fluid from sarcoidosis patients correlates with HLA‐DR3
Authors: Grunewald Johan , Janson Carl Harald , Eklund Anders , Öhrn Mary , Olerup Olle , Persson Ulla , Wigzell Hans 
Published: March 2007

AbstractThe α/β T cell receptor (TcR) V gene usage of bronchoalveolar lavage (BAL) lymphocytes and peripheral blood lymphocytes (PBL) from 11 sarcoidosis patients and 4 healthy controls was investigated, using eight α/β TcR V gene product‐specific monoclonal antibodies (mAb). Twenty‐seven percent (3/11) of the sarcoidosis patients had a highly significant increase in Vα2.3+CD4+ T lymphocytes in the bronchoalveolar space, while displaying normal frequencies of these T cells in peripheral blood. The reactivities with the remaining seven TcR mAb were normal. In the control group, no compartmentalization of any T cells was seen. Four of the patients expressed the HLA‐DR3 (w17), DQw2 haplotype. Interestingly, the three patients with distinct signs of compartmentalized Vα2.3+CD4+ T cells all expressed this HLA haplotype. Additionally, a fourth patient with pronounced, although less significant, accumulation of Vα2.3+CD4+ T cells in the lung, was also HLA‐DR3(w17), DQw2+. Expression of Vα2.3+CD4+ T cells in BAL of these patients correlated with clinical disease, as revealed on re‐analyzing the four patients after 6 months or longer. Predominant TcR Vα2.3 gene usage in compartmentalized CD4+ BAL T lymphocytes, linked to HLA‐DR3(w17), DQw2 haplotype, may thus indicate presence of a specific antigen localized to the lungs of sarcoidosis patients.
CD4 binding to major histocompatibility complex class II antigens induces LFA‐1‐dependent and ‐independent homotypic adhesion of B lymphocytes
Authors: Kansas Geoffrey S. , Cambier John C. , Tedder Thomas F. 
Published: March 2007

AbstractT helper cells recognize processed antigen (Ag) in the context of major histocompatibility complex (MHC) class II antigens present on the surface of B cells and other Ag‐presenting cells. This interaction is mediated through the T cell receptor complex with associate recognition of class II molecules by the CD4 molecule. In this study, the binding of a soluble recombinant CD4/Ig heavy chain fusion protein (CD4‐γ3) or monoclonal antibody (mAb) to class II antigens on human B cells was shown to induce rapid and specific homotypic adhesion of B cells and most B lymphoblastoid cell lines. mAb reactive with CD4 inhibited CD4‐γ3‐induced adhesion and a mutant B lymphoblastoid cell line deficient in class II antigens failed to respond. Induction of homotypic adhesion was dependent on energy metabolism and a functional cytoskeleton, and class II+ pre‐B cells did not exhibit adhesion in response to these stimuli, suggesting that cross‐linking of class II molecules generated a transmembrane signal and did not simply aggregate cells. In addition, MHC class II‐induced adhesion was Fc receptor independent, as 15 mAb of different Ig isotypes reactive with HLA‐D or HLA‐DQ gene products induced adhesion. Anti‐class II mAb and CD4‐γ3 were able to induce adhesion at concentrations as low as 10 ng/ml and 100 ng/ml, respectively. Suboptimal stimulation of B cell lines through HLA‐D antigens induced homotypic adhesion that was dependent on the activation of LFA‐1 (CD11a/CD18), and which could be blocked by specific mAb. However, at greater signal strengths, adhesion was not blocked by mAb against the known adhesion receptors, suggesting the induction of a novel adhesion pathway. Consistent with this, homotypic adhesion induced by engagement of MHC class II antigens was observed with LFA‐1‐deficient B cell lines, and was independent of CD49d or CD18 expression. Thus, the direct engagement of B cell class II antigens by CD4 is likely to generate transmembrane signals which trigger both LFA‐1‐dependent and LFA‐1‐independent adhesion pathways.
Interleukin 4 (IL) 4 up‐regulates gene and surface IL 1 receptor type I in murine T helper type 2 cells
Authors: Koch Karl‐Christian , Ye Ke , Clark Burton D. , Dinarello Charles A. 
Published: March 2007

AbstractThe T cell‐derived cytokine interleukin (IL)4 is known to increase the proliferative response of T cells stimulated with IL1. IL4 is also an autocrine growth factor for type II T helper cells (Th2) cells. In the present studies, we examined the effect of murine recombinant IL 4 on the expression of the IL 1 receptor type I (IL 1RtI) in murine Th2 cell lines at the mRNA and surface level. Using a specific anti‐murine IL 1RtI monoclonal antibody and flow microfluorometry, we found that IL 4 increased the surface expression of IL 1RtI in a dose‐dependent manner. In D10S cells, a subline of the Th2 cell line D10.G4.1, 50‐500 pg/ml IL 4 up‐regulated the receptor 1.8‐ to 3.2‐fold (p < 0.05). This up‐regulation was also seen at the mRNA level. The effect was not due to increased stability of the mRNA, since IL4 did not modify the half‐life of IL 1RtI mRNA. IL4 also up‐regulated IL 1RtI on CDC25 cells, another Th2 cell line. However, we did not observe an effect of IL 4 on gene expression of IL 1RtI in BALB/c 3T3 fibroblasts. IL2 and IL4 showed an additive effect in up‐regulating IL 1RtI and D10S cells. These studies indicate that IL4 up‐regulates IL 1RtI in murine Th2 cells by increasing gene expression for IL 1RtI without affecting mRNA stability. Thus, IL 4 production by Th2 cells may amplify the immune response via up‐regulation of IL 1RtI.
Age‐associated increase in number of CD4+CD8+ intestinal intraepithelial lymphocytes in rats
Authors: Takimoto Hiroaki , Nakamura Takao , Takeuchi Makoto , Sumi Yukiko , Tanaka Toshiyuki , Nomoto Kikuo , Yoshikai Yasunobu 
Published: March 2007

AbstractA significant number of CD4+CD8+ T cells were detected in intestinal intraepithelial lymphocytes (IEL) of various strains of rats including Wistar, WKA, BN, LEW and F344. The site of the CD4+CD8+ population in IEL increased with age in all strains we examined. Most IEL bearing CD8 expressed no CD5 antigen in young rats, while all CD4+CD8+ IEL and some of CD8+ IEL in aged rats were of CD5+CD45RB− phenotype. In germ‐free Wistar rats, age‐associated increase in the number of CD4+CD8+CD5+ IEL was not evident, indicating that stimulation by the intestinal microflora was important for expansion of the CD4+CD8+CD5+CD45RB− IEL. Aged athymic F344 nude rats contained appreciable numbers of CD4+ IEL and CD8+ IEL but few CD4+CD8+ IEL, suggesting that the CD4+CD8+ IEL may be derived from thymus‐dependent populations. Unlike a majority of CD4+CD8+ thymocytes bearing a low intensity of CD3/T cell receptor (TcR) α/β, the CD4+CD8+ T cells in IEL expressed a high intensity of CD3/TcR α/β on their surface. The CD4+CD8+ IEL appear to contribute to the spontaneous proliferation of the IEL in aged rats as assessed by tritiated thymidine incorporation after in vitro culture with medium only. These results suggest that with aging a unique CD4+CD8+ IEL may expand at a local site of the intestine under the influence of intestinal microflora and may contribute to the first line of defense against various pathogens in the epithelium.
The specificity of recognition of a cytotoxic T lymphocyte epitope
Authors: Burrows Scott R. , Rodda Stuart J. , Suhrbier Andreas , Geysen H. Mario , Moss Denis J. 
Published: March 2007

AbstractAn Epstein‐Barr virus (EBV)‐specific CD8+ cytotoxic T lymphocyte (CTL) clone (LC13) was shown to recognize the minimal peptide determinant FLRGRAYGL from the EBNA 3 antigen of the BL74 strain of EBV. The equivalent epitope from the B95‐8 strain (FLRGRAYGI) is not recognized when endogenously presented and the peptide is 15‐fold less active than FLRGRAYGL. A replacement set of peptides was synthesized in which each residue within FLRGRAYGL was sequentially replaced with all other genetically coded amino acids. These peptides were tested for their ability to sensitize target cells to lysis by LC13. Of the 171 single‐amino acid replacement peptides only 15 were more active than the peptide FLRGRAYGI. Five peptides had significantly greater activity than FLRGRAYGL and a peptide incorporating the most active of these single‐amino acid substitutions (HIRGRAYSL) induced lysis at concentrations approximately 30‐fold less than FLRGRAYGL. Simplified theoretical calculations based on this study suggest that CTL LC13 has a specificity for its target epitope of 1 in 4.7 × 1010. This represents the first complete analysis of the role of single amino acids within a minimum epitope on the specificity of CTL recognition.
The genetics of IgG4 deficiency: Role of the immunoglobulin heavy chain constant region and HLA loci
Authors: Gallina Roberto , Bottaro Andrea , Boccazzi Cleide , Delange Gerda , Danese Paola , Mazzola Gina , Amoroso Antonio , Demarchi Mario , Carbonara Angelo Oscar 
Published: March 2007

AbstractIgG4 deficiency is very common (1/400 in the Italian population) and provides a good model for analyzing the genetic factors involved in Ig subclass deficiencies. We have previously reported an association between some immunoglobulin heavy chain constant region (IGHC) polymorphisms and the IgG4 deficiency. The associated polymorphisms spanned the region between the GP and the G4 genes. A larger sample composed of 50 healthy blood donors with IgG4 deficiency (< 0.001 g/l IgG4), not carrying homozygous gene deletions, together with 82 first‐degree relatives is now examined. The results confirmed the association of the deficiency with IGHC polymorphisms, and detected a new association with the HLA‐D locus with a strong additive effect between the two systems. However, despite these associations and a highly significant risk for IgG4 deficiency within families, close linkage with either IGHC or HLA loci was not apparent by the affected sib pair method. These findings suggest that several concomitant, possibly cooperating, genetic factors may be involved in IgG4 deficiency.
Cloning and expression of an inducible lymphoid‐specific, protein tyrosine phosphatase (HePTPase)
Authors: Zanke Brent , Suzuki Haruhiko , Kishihara Kenji , Mizzen Lee , Minden Mark , Pawson Anthony , Mak Tak W. 
Published: March 2007

AbstractTyrosine phosphorylation and dephosphorylating events have been shown to be central to the process of growth regulation and signal transduction. We report here, the identification of a new gene with a tyrosine phosphatase domain (EC 3.1.3.48) which is expressed exclusively in thymus and spleen. A cDNA of 2760 bp encodes a 339‐amino acid, intracellular, single‐domain tyrosine phosphatase. When expressed as a glutathionine‐S‐transferase fusion protein, efficient lysis of p‐nitrophenyl phosphate is noted, indicating in vitro enzymatic activity of the cloned gene product. Normal mouse lymphocytes increase mRNA expression 10‐15‐fold upon stimulation with phytohemagglutinin, concanavalin A, lipo‐polysaccharide or anti‐CD3 monoclonal antibody. This new hematopoietic tyrosine phosphatase, (HePTP), may play a role in the regulation of T and B lymphocyte development and signal transduction.
Restricted utilization of germ‐line VH3 genes and short diverse third complementarity‐determining regions (CDR3) in human fetal B lymphocyte immunoglobulin heavy chain rearrangements
Authors: Raaphorst Frank M. , Timmers Erik , Kenter Marcel J. H. , Van Tol Maarten J. D. , Vossen Jaak M. , Schuurman Ruud K. B. 
Published: March 2007

AbstractTwenty‐one independent immunoglobulin heavy chain VH3DJH rearrangements were cloned and sequenced from livers of human fetuses at 7, 13 and 18 weeks of gestation. The VH elements expressed were not somatically mutated. Eight out of the estimated 30 VH3 elements were utilized with a preference for five of them. One of these VH3 sequences, designated FL13‐28, represented a thus‐far unknown VH3 gene segment. From the six functional JH elements the JH3 and JH4 segments were utilized preferentially and from the estimated 30 D segments the DQ52 element and the Dxp family were found to rearrange frequently. D elements were utilized both in normal and inverted orientation, as single copies or in D to D fusions. Addition of N nucleotides, removal of nucleotides from the coding sequences and utilization of DIR elements (D genes with irregular recombination signals) further expanded the third complementarity‐determining region (CDR3) diversity. One fourth of the fetal CDR3 regions lacked N regions. Due to utilization of DQ52, the relative absence of N regions and extensive exonuclease activity operating on the D elements, the fetal CDR3 regions were significantly shorter than those found in adult B lymphocytes.
Age‐associated changes in mitogen‐induced protein phosphorylation in murine T lymphocytes
Authors: Patel Hiren R. , Miller Richard A. 
Published: March 2007

AbstractSince T lymphocyte proliferation declines with age, and since activation of a still only partially defined set of protein kinases is thought to play a critical role in T cell activation, we have carried out a systematic survey of age‐related changes in protein phosphorylation in T lymphocytes. We used two‐dimensional electro‐phoretic analysis to examine lysates prepared from T cells after 10 min of exposure to mitogens [anti‐CD3, concanavalin A (Con A) and phorbol 12‐myristate 13‐acetate (PMA) plus ionomycin] and nonmitogenic activators (PMA or ionomycin used separately). Our results show a progressive, life‐long decline in the levels of anti‐CD3‐induced phosphorylation of all 16 phosphoproteins that respond vigorously in T cells of young mice. Mice 10‐18 months of age showed levels of response that were clearly below those induced in young mice, while responses of mice 22‐24 months of age were even more severely diminished. Responses to Con A, PMA, ionomycin and a combination of PMA plus ionomycin were equally blunted in old mice, except for 2 (of 12) phosphoproteins that continued to respond to PMA even in the old animals. None of the phosphoproteins which were ionomycin responsive in young mice continued to respond in old mice, although 1 (of 3) ionomycin‐inhibitable phosphoproteins remained inhibitable in old mice. We also found three phosphoproteins which became phosphorylated in response to anti‐CD3, PMA and Con A (but not ionomycin) only in old mice, and a pair of phosphoproteins which were unresponsive to all mitogens but showed a higher “baseline” phosphorylation in T cells from old mice.Comparing phosphoprotein patterns between CD8− and CD8−CD45RB− T cells from young mice allowed us to identify nine phosphoproteins that were strongly responsive to anti‐CD3 only when when CD45RB+ (i.e. virgin) cells were present. Although the immune system of old mice consists largely of memory T cells, the change in phosphoprotein phosphorylation patterns cannot simply be explained by the accumulation of this cell type. We conclude that aging leads to a global impairment of several distinct protein kinase pathways in both virgin and memory T cell sets.
Cell kinetics of the germinal center reaction ‐ a stathmokinetic study
Authors: Hollowood Kevin , Macartney James 
Published: March 2007

AbstractThe changes in splenic germinal center (GC) cell proliferation were measured during primary and secondary responses to a T‐dependent antigen in vivo to examine the regulation of the GC reaction. Adult C3H/HeN mice were immunized with sheep red blood cells and boosted 7 or 21 days later. GC cell proliferation was assessed by measurement of GC cell birth rates using a stathmokinetic technique. Actual GC growth and regression were assessed in terms of total splenic volume and number. Pre‐existing GC had a mean cell birth rate of 33 cells/1000 cells/h. The GC reactions following each immunization showed a biphasic pattern of changes in cell birth rate, comprising an initial fall immediately succeeded by a transient, but significant, increase. These fluctuations occurred earlier in secondary compared to primary responses. Significant increases in total GC volumes succeeded the peaks of cell birth rate following both primary and early secondary immunization. However, there was a substantially smaller increase following later secondary immunization. We propose that the initial cell birth rate reduction is due to inhibition of pre‐existing GC clones and represents one component of the phenomenon of GC dissociation. The succeeding peak birth rate represents early, massive proliferation of newly activated antigen‐specific clones. The different patterns of GC expansion, despite similar proliferative responses, may reflect different pathways of differentiation dependent on the timing of antigenic stimulation.
The human intraepithelial lymphocyte marker HML‐1 is an integrin consisting of a β7 subunit associated with a distinctive α chain
Authors: Cerf‐Bensussan Nadine , Bègue Bernadette , Gagnon Jean , Meo Tommaso 
Published: March 2007

AbstractThe membrane antigen defined by the monoclonal antibody (mAb) HML‐1 is abundantly expressed on, and largely restricted to, the T cells which populate the intestinal epithelium. We show that the mature form of the antigen is a heterodimer comprising a 150‐kDa α chain and a 120‐kDa β chain. Direct sequencing of tryptic peptides cleaved from the purified β chain identified this polypeptide with the integrin β7 isotype. cDNA clones coding for the β7 chain have recently been isolated from T cell cDNA libraries, but the β7 chain had not been identified at the protein level. No information is available concerning the primary structure of the HML‐1 α chain. We show that this subunit is synthesized as a precursor form that undergoes, like several other integrin α subunits, a post‐translational cleavage of a peptide bond. Among the 11 human integrin α chains previously identified, 10 have biochemical features and/or a distribution different from those of HML‐1 α. One, VLAα4 (CD49d), has a molecular mass of 150 kDa and is expressed on HML‐1+ cells but is not recognized by HML‐1 mAb. We conclude that HML‐1 is a novel member of the integrin family made of the β7 chain and of an as‐yet‐undescribed human α chain characterized by the post‐translational cleavage of a 10‐kDa peptide. HML‐1 is, thus, probably the human counterpart of the mouse antigen M290.