bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Fusobacterium nucleatum on the T and B cell responses to Porphyromonas gingivalis in a mouse model
Authors: GEMMELL E , BIRD P S , CARTER C L , DRYSDALE K E , SEYMOUR G J 
Published: March 2003

SUMMARY
T cell cytokine profiles and specific serum antibody levels in five groups of BALB/c mice immunized with saline alone, viable Fusobacterium nucleatum ATCC 25586, viable Porphyromonas gingivalis ATCC 33277, F. nucleatum followed by P. gingivalis and P. gingivalis followed by F. nucleatum were determined. Splenic CD4 and CD8 cells were examined for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma and IL-10 by dual colour flow cytometry and the levels of serum anti-F. nucleatum and anti-P. gingivalis antibodies determined by an ELISA. Both Th1 and Th2 responses were demonstrated by all groups, and while there were slightly lower percentages of cytokine positive T cells in mice injected with F. nucleatum alone compared with the other groups immunized with bacteria, F. nucleatum had no effect on the T cell production of cytokines induced by P. gingivalis in the two groups immunized with both organisms. However, the percentages of cytokine positive CD8 cells were generally significantly higher than those of the CD4 cells. Mice immunized with F. nucleatum alone had high levels of serum anti-F. nucleatum antibodies with very low levels of P. gingivalis antibodies, whereas mice injected with P. gingivalis alone produced anti-P. gingivalis antibodies predominantly. Although the levels of anti-F. nucleatum antibodies in mice injected with F. nucleatum followed by P. gingivalis were the same as in mice immunized with F. nucleatum alone, antibody levels to P. gingivalis were very low. In contrast, mice injected with P. gingivalis followed by F. nucleatum produced equal levels of both anti-P. gingivalis and anti-F. nucleatum antibodies, although at lower levels than the other three groups immunized with bacteria, respectively. Anti-Actinobacillus actinomycetemcomitans, Bacteroides forsythus and Prevotella intermedia serum antibody levels were also determined and found to be negligible. In conclusion, F. nucleatum immunization does not affect the splenic T cell cytokine response to P. gingivalis. However, F. nucleatum immunization prior to that of P. gingivalis almost completely inhibited the production of anti-P. gingivalis antibodies while P. gingivalis injection before F. nucleatum demonstrated a partial inhibitory effect by P. gingivalis on antibody production to F. nucleatum. The significance of these results with respect to human periodontal disease is difficult to determine. However, they may explain in part differing responses to P. gingivalis in different individuals who may or may not have had prior exposure to F. nucleatum. Finally, the results suggested that P. gingivalis and F. nucleatum do not induce the production of cross-reactive antibodies to other oral microorganisms.
Activation of human T cells with NK cell markers by staphylococcal enterotoxin A via IL-12 but not via IL-18
Authors: AMI K , OHKAWA T , KOIKE Y , SATO K , HABU Y , IWAI T , SEKI S , HIRAIDE H 
Published: March 2003

SUMMARYWe have reported recently that mouse liver NK cells and NK1·1+ T cells were activated by bacterial superantigens via the IL-12 production from Kupffer cells. In the present study, we examined the effect of staphyloccoccal enterotoxin A (SEA) on human T cells with NK cell markers, CD56 or CD57 (NK-type T cells). After stimulating peripheral blood mononuclear cells (PBMC) with SEA, PBMC produced a large amount of IFN-γ and acquired a potent antitumour cytotoxicity. The in vitro depletion of either CD56+ TCR– NK cells, CD56+ T cells or 57+ T cells from PBMC significantly inhibited the IFN-γ production from PBMC. When purified NK-type T cells, NK cells and regular T cells were cultured with monocytes and SEA they all produced IFN-γ, while the IFN-γ amounts produced by both NK-type T cells were greater than those produced by NK cells. NK cells as well as CD56+ T cells showed cytotoxicity against NK-sensitive K562 cells, whereas both NK-type T cells showed a more potent cytotoxicity against NK-resistant Raji cells than did NK cells. The IFN-γ production from each population as well as from whole PBMC was greatly inhibited by anti-IL-12 antibody but not by anti-IL-18 antibody. The antitumour cytotoxicity of whole PBMC was also significantly inhibited by anti-IL-12 antibody while the SEA-induced proliferation of PBMC was not affected by anti-IL-12 antibody. Furthermore, SEA-activated NK-type T cells as well as NK cells showed cytotoxicities against vascular endothelial cells. Our findings suggest that human NK-type T cells are thus involved in bacterial superantigen-induced immune response.
Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors
Authors: NAKATA A , OGAWA K , SASAKI T , KOYAMA N , WADA K , KOTERA J , KIKKAWA H , OMORI K , KAMINUMA O 
Published: March 2003

SUMMARYEven though the existence of phosphodiesterase (PDE) 7 in T cells has been proved, the lack of a selective PDE7 inhibitor has confounded an accurate assessment of PDE7 function in such cells. In order to elucidate the role of PDE7 in human T cell function, the effects of two PDE inhibitors on PDE7A activity, cytokine synthesis, proliferation and CD25 expression of human peripheral blood mononuclear cells (PBMC) were determined. Recombinant human PDE7A was obtained and subjected to cyclic AMP-hydrolysis assay. PBMC of Dermatophagoides farinae mite extract (Df)-sensitive donors were stimulated with the relevant antigen or an anti-CD3 monoclonal antibody (MoAb). PBMC produced IL-5 and proliferated in response to stimulation with Df, while stimulation with anti-CD3 MoAb induced CD25 expression and messenger RNA (mRNA) synthesis of IL-2, IL-4 and IL-5 in peripheral T cells. A PDE inhibitor, T-2585, which suppressed PDE4 isoenzyme with high potency (IC50 = 0·00013 μm) and PDE7A with low potency (IC50 = 1·7 μm) inhibited cytokine synthesis, proliferation and CD25 expression in the dose range at which the drug suppressed PDE7A activity. A potent selective inhibitor of PDE4 (IC50 = 0·00031 μm), RP 73401, which did not effectively suppress PDE7A (IC50 &gt; 10 μm), inhibited the Df- and anti-CD3 MoAb-stimulated responses only weakly, even at 10 μm. PDE7 may play a critical role in the regulation of human T cell function, and thereby selective PDE7 inhibitors have the potential to be used to treat immunological and inflammatory disorders.
Differential graft-versus-leukaemia effect by CD28 and CD40 co-stimulatory blockade after graft-versus-host disease prophylaxis
Authors: OHATA J , SAKURAI J , SAITO K , TANI K , ASANO S , AZUMA M 
Published: March 2003

SUMMARYCo-stimulatory blockade may be a promising strategy for tolerance induction in transplantation. In allogeneic bone marrow transplantation (BMT) for leukaemia treatment, however, preservation of the graft-versus-leukaemia (GVL) effect is another critical requirement for clinical application. In this study, we have compared the effect on GVL of using CD28 and CD40 co-stimulatory blockades as graft-versus-host disease (GVHD) prophylaxis in a murine allogeneic BMT model with simultaneous transfer of BCL1 leukaemia. Despite the relative improvement of GVHD as assessed by survival and body weight in both treatment regimes, treatment with anti-CD154 moAb clearly diminished the GVL effect, whereas treatment with anti-CD80 and CD86 MoAbs maintained this effect. Although T cell-mediated effector function at 14 days post-BMT assessed by IFNγ expression and cytotoxicity against host alloantigen was comparable between both co-stimulatory blockades, IL-12 mRNA expression was preferentially reduced by CD40 blockade. Our results suggest the differential involvement of the CD28 and CD40 co-stimulatory pathways in the development of GVHD and GVL effects. CD28 blockade may be a favourable strategy for tolerance induction in leukaemia patients undergoing BMT.
The molecular mechanism in activation-induced cell death of an Ag-reactive B cell clon
Authors: HAMANO T , IWASAKI T , OGATA A , HASHIMOTO N , KAKISHITA E 
Published: March 2003

SUMMARYTPA-1 is a subclone of B cell hybridomas established by somatic hybridization using B cells of A/J mice immunized with TNP-LPS, and expresses a receptor for TNP on the cell membrane. The present study showed that TPA-1 was induced to apoptotic cell death upon treatment with TNP-BSA. Therefore, TPA-1 is considered to provide a good model for the study on activation-induced cell death of mature B cells induced by soluble antigen. TNP-BSA treatment caused the generation of a large amount of intracellular reactive oxygen species (ROS) of TPA-1, and the addition of the monovalent thiol-reactive compound: monochlorobimane (MCB) rescued it from apoptosis as well as the antioxidant reagent: N-acetyl-l-cysteine. Furthermore, MCB markedly inhibited the generation of ROS and prevented the disruption of mitochondrial membrane potential that was induced by TNP-BSA treatment. In addition, it counteracted the effect of TNP-BSA on the expression of the Bcl-2 family, resulting in down-regulation of Bax and Bad and up-regulation of Bcl-XL. Taken together, these results suggest strongly that oxidative stress of mitochondria may be involved directly in apoptotic cell death by engagement of antigen receptors on mature B cells with soluble antigen.
Impaired up-regulation of CD70 and CD86 in naive (CD27−) B cells from patients with common variable immunodeficiency (CVID)
Authors: GROTH C , DRÄGER R , WARNATZ K , WOLFF-VORBECK G , SCHMIDT S , EIBEL H , SCHLESIER M , PETER H-H 
Published: March 2003

SUMMARYCVID is characterized by reduced serum levels of all switched immunoglobulin isotypes (IgG, IgA, IgE) predisposing patients to recurrent infections of their respiratory and gastrointestinal tract. Correspondingly, most CVID patients exhibit a severely decreased proportion of class switched memory B cells (CD19+CD27+IgD−IgM−IgG+ or IgA+) in their peripheral blood (CVID type I). We previously identified a subgroup of CVID patients showing a significantly reduced expression of CD86 and CD137 following activation in vitro of PBMC or purified B cells (CD19+) with anti-IgM plus IL-2. Here we extend our previous studies by asking whether highly purified, cell-sorted naive B cells show already an expression defect of B cell surface molecules relevant in activation (CD39, CD69), differentiation (CD24, CD27, CD38) or T–B interaction (CD25, CD70, CD86). We stimulated cell-sorted, naive B cells (CD19+CD27−IgM+IgDhighIgG−IgA−) from 10 CVID patients and 10 healthy controls for 4 days with anti-IgM plus IL-2 in the absence or presence of autologous CD4+ T cells and measured the expression of the referred surface molecules. Based on reduced or normal numbers of switched memory B cells the CVID patients had previously been classified into eight type I patients and two type II patients, respectively. Interestingly, only the molecules CD25, CD70 and CD86, all relevant in cognate T–B interaction, showed a significantly lower expression in naive B cells from CVID patients compared to controls. While coculture with autologous CD4+ T cells normalized the CD25 expression, CD70 and CD86 expression remained subnormal, notably in the eight CVID patients of type I. These findings strongly suggest an intrinsic signalling or expression defect for CD70/CD86 at the level of naive B cells in type I CVID patients.
Systemic treatment with anti-CD40 antibody stimulates Langerhans cell migration from the skin
Authors: JOLLES S , CHRISTENSEN J , HOLMAN M , KLAUS G B , AGER A 
Published: March 2003

SUMMARYEpidermal Langerhans cells (LCs) play a pivotal role in the initiation of cutaneous immune responses. The maturation of LCs and their migration from the skin to the T cell areas of draining lymph nodes are essential for the delivery and presentation of antigen to naïve T cells. CD40, which acts as a costimulatory molecule, is present on LCs and the basal layer of keratinocytes in the skin. We show here that systemic treatment of mice with anti-CD40 antibody stimulates the migration of LCs out of the epidermis with a 70% reduction in LC numbers after 7 days, although changes in LC morphology are detectable as early as day 3. LC numbers in the epidermis returned to 90% of normal by day 21. As well as morphological changes, LC showed up-regulated levels of Class II and ICAM-1, with only minimal changes in CD86 expression 3 days following anti-CD40 treatment. Despite increased levels of Class II and ICAM-1, epidermal LC isolated from anti-CD40 treated mice were poor stimulators of a unidirectional allogeneic mixed leucocyte reaction (MLR), as were epidermal LC isolated from control mice. These results indicate that CD40 stimulation is an effective signal for LC migration, distinct from maturation of immunostimulatory function in the epidermis, which is not altered. These observations may have important implications for the mechanism of action of agonistic anti-CD40 antibodies, which have been used as an adjuvant in models of infection and experimental tumours and the primary immunodeficiency Hyper IgM syndrome caused by deficiency of CD40 ligand.
T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking
Authors: KIVISÄKK P , TREBST C , LIU Z , TUCKY B H , SØRENSEN T L , RUDICK R A , MACK M , RANSOHOFF R M 
Published: March 2003

SUMMARYIt is believed that chemokines and their receptors are involved in trafficking of T-cells to the central nervous system (CNS). The aim of the current study was to define the expression on cerebrospinal fluid (CSF) T-cells of six chemokine receptors associated with trafficking to sites of inflammation. Flow cytometry was used to detect chemokine receptor expression. We observed that CD3+T-cells in the CSF express a restricted array of inflammatory chemokine receptors, specifically CXCR3, CCR5 and CCR6, but little CCR1-3. This repertoire was independent of the presence of CNS inflammation, since comparable findings were obtained in patients with multiple sclerosis (MS) and individuals with non-inflammatory neurological diseases. The enrichment of CCR5+T-cells in the CSF could largely be explained by higher frequency of CD4+/CD45RO+T-cells in this compartment. In contrast, CD4+/CD45RO+T-cells expressing CXCR3 were significantly enriched in CSF as compared with blood. Similar levels of CCR6+/CD3+T-cells were observed in blood and CSF, while levels of CCR2+/CD3+T-cells were lower in CSF than in blood. The CSF was virtually devoid of CCR5+/CXCR3- T-cells, suggesting that the expression of CCR5 alone is not sufficient for the trafficking of CD3+T-cells to the CSF. We hypothesize that CXCR3 is the principal inflammatory chemokine receptor involved in intrathecal accumulation of T-cells in MS. Through interactions with its ligands, CXCR3 is proposed to mediate retention of T-cells in the inflamed CNS.
The immunology of primary biliary cirrhosis: the end of the beginning?
Authors: PALMER J M , KIRBY J A , JONES D E J 
Published: March 2003

SUMMARYThe chronic liver disease primary biliary cirrhosis (PBC) is characterised by autoreactive B-cell and T-cell responses directed against mitochondrial antigens. In recent years these responses have been extensively characterised and the principal PBC associated autoantigen identified as pyruvate dehydrogenase complex (PDC). The identification of anti-PDC responses (present in over 95% of PDC patients) has given rise to important questions pertinent to our understanding of the pathogenesis of PBC. What specific role to anti-PDC responses play in target cell damage? How and why does immune tolerance break down to as highly conserved and ubiquitously expressed self-antigen as PDC? Why does breakdown in tolerance to an antigen present in all nucleated cells result in damage restricted to the intra-hepatic bile ducts? In attempting to answer these key questions we have, in this review, proposed a unifying hypothesis for the pathogenesis of PBC.
Ribavirin increases mitogen- and antigen-induced expression of CD40L on CD4+ T cellsin vivo
Authors: BERGAMINI A , CEPPARULO M , BOLACCHI F , ARACO A , TISONE G , OMBRES D , ROCCHI G , ANGELICO M 
Published: March 2003

SummaryHere, CD40L expression and cytokine production have been analysed in peripheral blood cells from orthotopic liver transplantation (OLT) recipients treated with ribavirin for recurrent chronic hepatitis C. The study included 18 OLT recipients treated with ribavirin, eight control OLT recipients and 10 healthy controls. FACS analysis showed that baseline expression of CD40L was not different between ribavirin-treated patients and controls. In contrast, after stimulation with both HCV core antigen and phorbol myristate acetate (PMA) plus ionomycin (IO), the expression of CD40L on CD4 lymphocytes was significantly higher in the ribavirin group compared with controls. In the ribavirin group, the increased expression of CD40L significantly correlated with reduction of HCV RNA levels with respect to pretreatment values. Finally, ribavirin treatment was not associated with modification of PMA-IO-induced cytokine production by T lymphocytes and interleukin (IL)-1β and tumour necrosis-α (TNF)-α production by CD40L-stimulated monocytes. In conclusion, these data indicate that ribavirin ­upmodulates CD40L expression on CD4 T cells, a property which may account in part for its ability to enhance the antiviral activity of interferon-α in the treatment of chronic HCV infection.
Impact of NNRTI compared to PI-based highly active antiretroviral therapy on CCR5 receptor expression, β  -chemokines and IL-16 secretion in HIV-1 infection
Authors: BURTON C T , HARDY G A D , SULLIVAN A K , NELSON M R , GAZZARD B , GOTCH F M , IMAMI N 
Published: March 2003

Summary
Interleukin-16 (IL-16) and the β-chemokines (RANTES, monocyte chemotactic protein-1 (MCP-1), macrophage inhibitory protein (MIP)-1α and (MIP)-1β) are soluble in vitro suppressors of macrophage tropic HIV-1 strains. The reduction of HIV-1 RNA plasma levels in late-stage patients receiving protease inhibitors has been associated with increased concentrations of MIP-1α, MIP-1β, RANTES and IL-16 and a decrease in levels of MCP-1. We determined plasma levels of MCP-1, MIP-1α, MIP-1β, RANTES and IL-16 during the first 16 weeks of highly active antiretroviral therapy (HAART) in chronic HIV-1-infected patients. Patients were administered one of two therapeutic regimens based on either   a   protease   inhibitor (PI) or   a   non-nucleoside   reverse   transcriptase    inhibitor (NNRTI).   No differences were seen in the levels of RANTES and IL-16 over the first 16 weeks of HAART in either treatment group. MCP-1 decreased significantly in the PI-treated group over the first 16 weeks of HAART (P = 0·0003). A significant increase was observed in the levels of MIP-1α and MIP-1β in the NNRTI cohort (P = 0·0010 and P = 0·0012, respectively). A significant decrease in levels of MIP-1α and MIP-1β (P = 0·0015 and P = 0·0299, respectively) was observed over the 16 weeks in the PI cohort. A significant difference was seen when the levels of MIP-1α and MIP-1β were compared between the NNRTI and the PI cohorts at week 16 (P = 0·04 and P = 0·05, respectively). Evaluation of CCR5 expression ex vivo revealed no difference between the two treatment groups. Patients were genotyped for CCR5 Δ32 and the incidence of heterozygosity was lower than in the HIV-1 seronegative controls (3% compared to 19%).
Detection and characterization of plasma cells in peripheral blood: correlation of IgE+ plasma cell frequency with IgE serum titre
Authors: HORST A , HUNZELMANN N , ARCE S , HERBER M , MANZ R A , RADBRUCH A , NISCHT R , SCHMITZ J , ASSENMACHER M 
Published: March 2003

SummaryIn atopic patients and patients with hyper-IgE syndrome (HIE) highly elevated IgE serum levels can be detected. Due to their very low frequency little is known about IgE-producing plasma cells (PC) in peripheral blood. We used CD138 MACS microbeads to enrich plasma cells from peripheral blood of normal donors, atopic patients and one HIE patient. CD138+ cells were mainly CD45+, CD44++, CD19dim, CD38++, CD27++, CD86+, HLA-DR+/++, CD71dim, VLA-4+, VLA-5–, CD28–, CD25–, CD69–, CLA–, CD20–, CD21– and CD22–. They show weak expression of surface Ig but high levels of intracellular Ig and they secrete Ig in culture. Thus CD138+ cells from peripheral blood show characteristics of early plasma cells. IgE+ CD138+ plasma cells could be detected in 19 of 24 normal donors with an average frequency of 0·06% IgE+ cells among CD138+ cells. Higher frequencies were detected in atopic patients, atopic patients with markedly elevated serum IgE levels and the hyper-IgE patient with an average of 0·32%, 7·21% and 6·54%, respectively. Additionally, using the recently developed cellular affinity matrix technology, we were able to detect IgE secreting plasma cells and thereby could demonstrate that most of the IgE secreting cells express CD138. The frequency of IgE+ CD138+ cells among PBMC correlated highly significantly with serum IgE titres (r = 0·8532***), indicating that IgE secreting CD138+ cells in peripheral blood are directly related to the plasma cell pool contributing to the IgE titre.
Monocytes are primed to produce the Th1 type cytokine IL-12 in normal human pregnancy: an intracellular flow cytometric analysis of peripheral blood mononuclear cells
Authors: SACKS G P , REDMAN C W G , SARGENT I L 
Published: March 2003

SummaryThis paper considers both monocytes and peripheral blood lymphocytes as potential targets for maternal immunological modulation in pregnancy. Peripheral blood mononuclear cells (PBMCs) from non-pregnant and normal pregnant donors were stimulated in vitro, and cytokine production detected intracellularly by flow cytometry. It was found that monocyte production of TNF-α was unaltered in pregnancy, while production of IL-12 was significantly enhanced. In contrast, production of the Th1 type cytokine IFN-γ was suppressed in the lymphocyte subsets: CD4+ T helper cells and CD56+ NK cells. Production of the Th2 type cytokine IL-4 in CD4+ cells was not significantly altered in pregnancy. These data suggest that the concept that pregnancy is a ‘Th2 phenomenon’ cannot be generalized to the function of all aspects of maternal cellular immunity as, paradoxically, circulating monocytes are ‘primed’ to produce the Th1 cytokine IL-12. Furthermore, these data support the hypothesis that components of maternal innate immunity are activated in normal pregnancy.