bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective stimulation of murine cytotoxic T cell and antibody responses by particulate or monomeric hepatitis B virus surface (S) antigen
Authors: Schirmbeck Reinhold , Melber Karl , Mertens Thomas , Reimann Jörg 
Published: March 2007

AbstractIn the murine system, we tested in vivo the immunogenicity of different preparations of the yeast‐derived surface antigen (S‐antigen or S‐protein) of hepatitis B virus (HBV). Native S‐protein molecules self‐assemble into stable 22‐nm particles. BALB/c mice immunized with low doses of native S‐particles without adjuvants efficiently generated an H‐2 class I‐restricted CD8+ cytotoxic T lymphocyte (CTL) response, and developed easily detectable serum antibody titers against conformational determinants of the native S‐particle or linear epitopes of the denatured S‐protein. Disruption of S‐particles with sodium dodecyl sulfate and β‐2‐mercaptoethanol generated p24 S‐monomers. Injection of an equal dose of S‐monomers into mice efficiently primed CTL, but did not stimulate an antibody response against conformational or linear epitopes of the native or denatured S‐protein. In vivo priming of CTL by S‐particles or S‐monomers required “endogenous” processing of the antigen because the injection of an equimolar (or higher) dose of an antigenic, S‐derived 12‐mer peptide into mice did not prime CTL. Native (particulate) or denatured (monomeric) S‐antigen injected with mineral oil (incomplete Freund's adjuvant) or aluminum hydroxide failed to stimulate a CTL response. Hence, different preparations can be produced from a small protein antigen which specifically stimulate selected compartments of the immune system.
Allergen‐induced CD23 on CD4+ T lymphocytes and CD21 on B lymphocytes in Patients with allergic asthma: Evidence and regulation
Authors: Gagro Alenka , Rabatić Sabina 
Published: March 2007

AbstractInteraction of CD4+ T cells and B cells is necessary for IgE production. It has been recently demonstrated that cell surface antigen CD21 is a ligand for CD23 (FcϵRII) and that the pairing of these molecules may participate in the control of IgE production. In this study we investigated the effect of the Dermatophagoides pteronyssinus (Dpt) allergen and recombinant interleukin(rIL)‐4 on the expression of CD21 and CD23 on T and B cells of asthmatic patients allergic to Dpt and of healthy controls. Peripheral blood mononuclear cells (PBMC) were incubated alone or with Dpt allergen (100 biological units/ml) and/or rIL‐4 (100 U/ml) for up to 7 days. The flow‐cytometric analysis of double‐fluorescence staining revealed that Dpt allergen and/or rIL‐4 induced CD23 on CD4+ T lymphocytes only in allergic patients. The allergen‐induced CD23 on T cells is de novo synthesized antigen since no induction of CD23 on T cells was observed in cultures with 0.4 μg/ml actinomycin D. Moreover, 100 U/ml of interferon‐γ inhibited the induction of CD23 on CD4+ T cells. T cells obtained from healthy donors did not express CD23 or CD21 antigen upon incubation with allergen and/or rIL‐4. Although rIL‐4 also induced CD23 in controls, the expression was only observed on CD20+ cells. The allergen alone induced a significant elevation of the mean fluorescence intensity of both CD21 and CD23 only in allergic in dividuals. When the cell proliferation was analyzed, a slightly increased stimulation index upon cultivation of PBMC was obtained from non‐allergic donors as well, but less than in allergic patients. The co‐expression of major histocompability complex class II molecules and CD23 on CD4+ T lymphocytes in allergic patients, as assessed by the three‐color immunofluorescence analysis, indicates that these cells were activated.We conclude that CD4+ T lymphocytes possess a unique capability to express CD23 upon exposure to allergen. Moreover, the allergen‐mediated induction of CD23 on T cells observed only in allergic patients may be the reason for the increase of IgE production. This would not occur in non‐allergic individuals as there is no CD23 expression on T cells.
The biased Vγ gene usage in the synovial fluid of patients with rheumatoid arthritis
Authors: Kageyama Yasunori , Koide Yukio , Miyamoto Shigehito , Inoue Tetsuo , Yoshida Takato O. 
Published: March 2007

AbstractTaking advantage of the reverse transcriptase‐polymerase chain reaction (RT‐PCR), we have analyzed T cell receptor γ‐chain mRNA of synovial fluid γ/δ T cells from patients with rheumatoid arthritis (RA) in comparison with those of peripheral blood mononuclear cells (PBMC) from RA patients and healthy individuals. The quantitative RT‐PCR method in conjunction with nucleotide sequencing revealed the frequent usage of the Vγ3 gene segment in RA synovial fluid mononuclear cells (SFMC) (p < 0.01) which in PBMC of healthy individuals occurred rarely. PBMC of most healthy individuals expressed the Vγ9 gene predominantly (p < 0.01) as expected. However, only half of RA patients showed elevated levels of the Vγ9 gene expression in their PBMC. The γ‐chain mRNA containing the Vγ3 gene in RA SFMC showed no conserved junctional sequence (complementarity‐determining region 3). To investigate the nature of ligands recognized by the Vγ3‐bearing T cells, we analyzed Vγ gene usage of RA SFMC, RA PBMC, and normal PBMC stimulated with Mycobacterium tuberculosis (MT) or MT plus interleukin‐2 since there is mounting evidence of high reactivity of RA SFMC to MT and mycobacterial heat‐shock protein 65. However, the Vγ usage appeared to be mostly Vγ9 in RA SFMC, RA PBMC and normal PBMC. Taken together these results suggest that an as yet unknown antigen(s) (other than MT) might select γ/δ T cells expressing the Vγ3 gene in RA SFMC.
Sialyl Lewisx‐ and L‐selectin‐dependent site‐specific lymphocyte extravasation into renal transplants during acute rejection
Authors: Turunen Juha Pekka , Paavonen Timo , Majuri Marja‐Leena , Tiisala Sinikka , Mattila Pirkko , Mennander Ari , Gahmberg Carl G. , Häyry Pekka , Tamatani Takuya , Miyasaka Masayuki , Renkonen Risto 
Published: March 2007

AbstractKidney allograft rejection is an inflammatory process dominated by lymphocytes. During rejection lymphocytes preferentially adhere to the peritubular capillary endothelium (PTCE), which acquires morphological features common to high endothelium. These observations indicate that PTCE is the site of lymphocyte entry into the rejecting renal allograft. Of the identified endothelial adhesion molecules, ICAM‐1 was already expressed on the endothelium of normal kidneys, and its expression was strongly enhanced during rejection without site‐specific restriction. VCAM‐1 was not expressed on the endothelium of normal or syngeneic kidneys, but its expression was induced during allograft rejection not only in PTCE, but occasionally also on the endothelium of larger vessels. Sialyl Lewisx (sLex) showed a very restricted pattern of expression; endothelium was sLex‐negative both in control and syngeneic kidneys. On the other hand, PTCE reacted strongly with anti‐sLex antibody in allografts. When kidney frozen sections were treated with sialidase the binding of lymphocytes decreased by 70%. Low‐dose chymotrypsin treatment of lymphocytes, known to remove L‐selectin from the lymphocyte surface, decreased their binding to PTCE by 60%. Likewise lymphocyte adhesion to PTCE was inhibited by 70% by anti‐sLex‐ and anti‐L‐selectin‐antibodies and by sLex tetrasaccharide. Finally PTCE in the allografts, but not in syngeneic grafts or normal kidneys, bound an L‐selectin‐IgG fusion protein, indicating that ligands for L‐selectin were induced during rejection.
Interferon‐γ‐ and interleukin‐4‐producing T cells can be primed on dendritic cells in vivo and do not require the presence of B cells
Authors: Ronchese Franca , Hausmann Barbara , Gros Graham Le 
Published: March 2007

AbstractThe antigen‐presenting cell (APC) requirements for the in vivo induction of Th1‐and Th2‐type responses were investigated using a severe combined immunodeficiency (SCID)mouse chimera model. SCID mice adoptively transferred with either T cells [SCID(T)] or T + B cells [SCID(T + B)] and immunized with antigen in adjuvant were able to generate antigen‐specific T cells which could produce both interferon (IFN)‐γ and interleukin (IL)‐4 upon in vitro restimulation. This suggests that B cell APC are not necessary for the priming of either IFN‐γ‐ or IL‐4‐producing T cells in vivo. The ability of different APC to activate Th2‐dependent effector mechanisms was also investigated. SCID(T) and SCID(T + B) mice were infected with the nematode parasite Nippostrongylus brasiliensis and analyzed for the development of IL‐5‐dependent peripheral blood eosinophilia. Following infection both SCID(T) and SCID(T + B) mice generated similar numbers of peripheral blood eosilnophils, suggesting that similar amounts of IL‐5 had been produced. Therefore, B cell APC are also not required for the in vivo activation of Th2 cells to lymphokine production. To establish more precisely which APC prime T cells to produce IFN‐γ and IL‐4, normal mice were immunized by injection of syngeneic splenic dendritic cells which had been pulsed with antigen in vitro. T cells from these immunized mice were able to produce good IFN‐γ and IL‐4 responses upon in vitro restimulation with specific antigen; therefore, dendritic cells appear to be sufficient APC for the in vivo priming of both IFN‐γ‐ and IL‐4‐producing T cells.
A specific intercellular pathway of apoptotic cell death is defective in the mature peripheral T cells of autoimmune lpr and gld mice
Authors: Gillette‐Ferguson Illona , Sidman Charles L. 
Published: March 2007

AbstractHomozygosity for either of the unlinked murine autosomal recessive mutations lpr or gld leads to autoimmunity characterized by peripheral accumulation of CD4−/CD8− “double‐negative” T cells, autoantibodies and various forms of tissue pathology. Recently, the gene affected by lpr was identified as fas, whose product acts as a trigger for programmed cell death or apoptosis. Data reported here indicate that the Fas receptor and its ligand, the wild‐type form of the gld gene product, are essential for antigen‐stimulated peripheral T cell apoptosis. Furthermore, the wild‐type gld gene product is a non‐cell‐autonomous protein that is produced by activated T cells. Apoptotic elimination of antigen‐receptor‐triggered peripheral T cells appears to be abnormal in lpr and gld mice, and this deficiency causes peripheral T cells to accumulate resulting in lymphadenopathy. These findings support the importance of apoptotic regulation of lymphocyte persistence after antigen encounter in vivo.
Anergic B cells constitutively present self antigen: Enhanced immunoglobulin receptor‐mediated presentation of antigenic determinants by B cells is hierarchical
Authors: Kanost Dawn , McCluskey James 
Published: March 2007

AbstractPresentation of hen egg lysozyme (HEL) by HEL‐specific B cells was studied in transgenic mice expressing anti‐HEL immunoglobulin (Ig‐transgenic). In T hybridoma assays, presentation of the HEL46–61 determinant by B cells from Ig‐transgenic mice required 103−104‐fold lower concentrations of HEL than were required for presentation by B cells from non‐transgenic mice. In contrast, presentation of the HEL determinants 112–129 and 25–43 by HEL‐specific B cells was either not significantly enhanced, or enhanced only 10‐fold compared with B cells from non‐transgenic mice. Enhanced presentation of HEL determinants by B cells from Ig‐transgenic donors was specific for HEL, since keyhole limpet hemocyanin or synthetic HEL46–61 peptide were presented comparably by B cells from Ig‐transgenic mice and non‐transgenic littermates. A minimum of 1–4% Ig‐transgenic B cells was required to detect enhanced presentation of HEL46–61 in vitro. Constitutive presentation of the HEL46–61 determinant, but not the HEL25–43 or HEL112–129 determinants, was detectable on anergic HEL‐specific B cells from double (HEL/Ig)‐transgenic mice. In the presence of exogenously added HEL, anergic B cells presented all three HEL determinants. Constitutively presented HEL46–61 was not due to endogenous synthesis of HEL antigen by anergic B cells from double‐transgenic mice, as comparable levels of the HEL46–61 determinant were constitutively presented by B cells from Ig‐Tg → HEL‐Tg irradiation bone marrow chimeric mice. Firstly, these results indicate that the enhanced antigen presentation mediated by Ig receptors on B cells is not equivalent for all antigenic determinants. Secondly, the data demonstrate that anergic, autoreactive B cells efficiently process and present nominal antigens in addition to constitutively presenting specific self antigen in vivo.
The Y chromosome‐linked “autoimmune accelerating” yaa gene suppresses collagen‐induced arthritis
Authors: Jansson Liselotte , Holmdahl Rikard 
Published: March 2007

AbstractThe Y‐linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease. We have investigated the role of the yaa gene in the development of the type II collagen (CII)‐induced arthritis (CIA), which is used as a model for rheumatoid arthritis. In contrast to the accelerating effects on development of lupus autoimmunity we can show that the presence of BXSB Y chromosome carrying the yaa gene block development of CIA in F1 crosses with three normally CIA‐susceptible strains, DBA/1, C3H.Q and B10.Q. Backcross experiments showed an additional modulatory effect from other BXSB genes or possibly from DBA/1 × chromosome. To evaluate the effect mediated by the yaa gene alone, the BXSB Y chromosome was bred into the DBA/1 gene background. The DBA/1 congenic DBA/1.yaa male mice were less susceptible to arthritis development than their DBA/1 counterparts. (B10.QxDBA/1.yaa)F1 acquired resistance to arthritis development similar to that of DBA/1.yaa, indicating a role for the yaa gene alone. The serum levels of autoantibodies to CII were significantly suppressed in all strains carrying yaa. In DBA/1.yaa mice a reduced number of T cells were found to produce interferon‐γ after in vitro stimulation with CII. Thus, although autoreactive B cells are important in both diseases they play different roles in murine lupus and in CIA.
Changes in thymic export of L‐selectin+ γδ and αβ T cells during fetal and postnatal development
Authors: Witherden Deborah A. , Abernethy Nevin J. , Kimpton Wayne G. , Cahill Ross N. P. 
Published: March 2007

AbstractWe have used the technique of in situ intrathymic injection of fluorescein isothiocyanate to examine L‐selectin expression on γδ and αβ T cells immediately after emigrating from the thymus of fetal and postnatal animals. We found that the percentage of L‐selectin+ thymocytes exported per day decreased by half after birth and that the export of T cells from the thymus does not rely on expression of the peripheral lymph node homing receptor, L‐selectin. Analysis of L‐selectin on emigrant and mature T cell subsets revealed a remarkable heterogeneity of expression, both in terms of the numbers of cells expressing this molecule as well as the level of expression. γδ T cells, reportedly not having a propensity for homing to lymph nodes, not only contained the highest proportion of L‐selectin+ cells, but also expressed far more of this molecule than either CD4+CD8− or CD4−CD8+ αβ T cells. Furthermore, those emigrant T cells expressing L‐selectin are somewhat immature in their expression of this molecule. Subsequent maturation resulted in up‐regulation of L‐selectin on mature peripheral blood T cells, maturation that was clearly independent of extrinsic antigen. This antigen‐independent post‐thymic maturation appeared to occur as part of the normal progression from immature thymocyte to mature peripheral T cell in both fetal and postnatal animals.
CD45RB expression defines two interconvertible subsets of human CD4+ T cells with memory function
Authors: Horgan Kevin J , Tanaka Yoshiya , Luce Gale E. Ginther , Van Seventer Gijs A. , Nutman Thomas B. , Shaw Stephen 
Published: March 2007

AbstractReciprocal expression of CD45RA and CD45RO in human CD4+ T cells defines populations understood to be naive cells (CD45RA+CD45RO−) and memory cells (CD45RA−CD45RO+). We investigate two subsets of CD45RA−CD45RO+ CD4+ human T cells which differ by fourfold in their expression of the CD45RB isoform; one is CD45RBbright and the other is CD45RBintermediate. In contrast, CD45RA+ naive cells are all CD45RBbright. Both subsets of CD45RA− cells proliferate in response to recall antigens so we designate them MEM 1 (CD45RO+RBbright) and MEM 2 (CD45RO+RBintermediate). CD45RA and CD45RB expression are regulated independently during in vitro activation of naive cells. When MEM 1 cells are activated they tend to down‐regulate CD45RB expression, whereas activated MEM 2 cells tend to up‐regulate CD45RB expression. Thus, in contrast to the stability of the CD45RA−CD45RO+ phenotype, the MEM 1 and MEM 2 phenotypes are labile and may interconvert. MEM 1 and MEM 2 cells produced comparable amounts of interleukin(IL)−2, IL−4, and IL‐5 though MEM 1 cells produced slightly more interferon(IFN)‐γ (mean 1.7‐fold more). MEM 1 cells consistently proliferated more (mean 2.3‐fold more) than MEM 2 cells early during in vitro activation. Thus, differential expression of CD45RB within CD45RA− cells defines two subsets that have similar properties except for somewhast greater IFN‐γ production and proliferative responses by MEM 1 cells. Variability in CD45RB expression may represent a mechanism for fine‐tuning the responsiveness of memory cells in vivo.
Activation and internalization of p56lck upon CD45 triggering of Jurkat cells
Authors: Marie‐Cardine Anne , Maridonneau‐Parini Isabelle , Fischer Siegmund 
Published: March 2007

AbstractRelationships between CD45 and p56Ick have been suggested by co‐immunoprecipitation of both proteins and by dephosphorylation of the p56lck regulatory site, Tyr 505, by CD45 in vitro. We investigated whether the kinase activity of p56lck is modulated in T cells triggered via CD45. We showed that incubation of Jurkat cells with a combination of two anti‐CD45 monoclonal antibodies (mAb) (MC5/2 + D3/9) induced an increase in p56lck kinase activity, while a single mAb did not. Under these conditions, p56lck underwent two consecutive waves of activation. This was accompanied by internalization of the kinase and by a time‐dependent increased accessibility of CD45 phosphatase at the plasma membrane. Similarly, activation and internalization of p56lck were observed using a combination of anti‐CD45 (MC5/2) and anti‐CD2(T112) mAb, suggesting that a functional complex consisting of CD45, CD2 and p56lck was formed upon cell triggering. Taken together, these results suggests that: (i) CD45 participates in the regulation of p56lck kinase activity in vivo and that (ii) CD45 could play a mediator role in the stimulation and endocytosis of p56lck through the CD2 pathway.
Differential expression of lymphocyte homing receptors by human memory/effector T cells in pulmonary versus cutaneous immune effector sites
Authors: Picker Louis J. , Martin Richard J. , Trumble Anne , Newman Lee S. , Collins Patricia A. , Bergstresser Paul R. , Leung Donald Y. M. 
Published: March 2007

AbstractThe heterogeneous expression of lymphocyte homing receptors (HR) by the (CD45RAlow/ROhigh) memory/effector T cell population in the human is thought to define subsets with tissue‐selective recirculatory potential. To investigate further the localization characteristics of these T cells, we used multiparameter flow cytometry to quantitate T cell subsets defined by expression of the skin‐selective HR called the cutaneous lymphocyte‐associated antigen (CLA), the peripheral lymph node (PLN) HR L‐selectin, the mucosal‐associated HR α4β7‐integrin, and the mucosal‐associated adhesion molecule αeβ7‐integrin in either cutaneous or pulmonary immune effector sites and corresponding peripheral blood. Compared to peripheral blood, skin T cells were highly enriched for the CLA+/L‐selectin+/αeβ7‐integrin− memory/effector subset, whereas lung memory/effector T cells were predominantly CLA−to low L‐selectin−, and almost half were αeβ7‐integrin+. α4β7‐integrin expressing memory/effector T cells were diminished in both skin and lung, suggesting that this HR is not a major participant in determining localization specificity in either of these sites. The characteristic pulmonary T cell HR phenotype did not significantly differ between the normal subjects and those with pulmonary inflammatory disease, and did not correlate with markers of T cell activation. Induction of a rapid up‐regulation of pulmonary inflammation via intrabronchial allergen challenge in asthmatic patients tended to decrease localization specificity, resulting in a more general importation of memory/effector subsets. Taken together, these results suggest that tissue microenvironments play a major role in determining the character of local T cell infiltrates via their ability to import and retain memory/effector subsets selectively or, more generally, depending on the intensity of local inflammatory stimuli.
Exogenous peptide ligand influences the expression and half‐life of free HLA class I heavy chains ubiquitously detected at the cell surface
Authors: Carreno Beatriz M. , Hansen Ted H. 
Published: March 2007

AbstractA pool of free HLA class I chains has been detected at the plasma membrane of all cells concomitantly expressing folded and assembled class I molecules. To determine the origin of these free HLA heavy chains, we have examined the biosynthesis of a single HLA class I molecule, HLA‐B27, expressed by a murine cell line (L‐B27). In L‐B27 cells, as previously shown in Epstein‐Barr virus‐transformed lymphoblastoid cell lines, a precursor/product relationship exists, early in biosynthesis, between free (HC10‐reactive) and beta‐2‐microglobulin (β2m)‐associated (W6/32‐reactive) class I heavy chains as demonstrated by pulse/chase experiments. At later stages in class I biosynthesis, both HC10‐ and W6/32‐reactive heavy chains display complex oligosaccharides and accumulate at the cell surface. HC10‐ and W6/32‐reactive molecules are both very stable at the cell surface, with half‐lifes (t1/2) of > 7 h and ∼ 4 h, respectively. Interestingly, cell surface expression and turnover of HC10‐ and W6/32‐reactive molecules were affected by the addition of peptide ligands to the culture media. Culturing cells in the presence of HLA‐B27 ligands resulted in the increased expression of W6/32‐reactive molecules and the decreased expression of HC10‐reactive molecules. Moreover, addition of exogenous peptide extended the t1/2 of W6/32‐reactive molecules to > 7 h and reduced that of HC10‐reactive molecules to 4 h. These results indicate that surface HC10‐reactive molecules result largely from W6/32‐reactive molecules following peptide and β2m dissociation. Therefore, HC10‐reactive species are not only the precursors but also the end products in class I biosynthesis.