bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of perforin on HIV-1-specific CD8+ lymphocytes after immunization with a gp120-depleted, whole-killed HIV-1 immunogen
Authors: Moss R B , Giermakowska W K , Wallace M R , Jensen F C , Maigetter R Z , Carlo D J 
Published: March 2003

SUMMARYWe examined HIV-1 antigen specific intracellular expression of perforin on CD4+ and CD8+ lymphocytes in subjects with chronic HIV-1 infection on antiviral drug therapy after immunization with a gp120-depleted, whole killed HIV-1 immunogen (inactivated, gp120-depleted HIV-1 in IFA, Remune). Based upon previous results, we hypothesized that the restoration of adequate T helper immune responses by vaccination against HIV-1 could result in the augmentation of CD8+ lymphocyte immune responses measured as perforin expression. In the current study we observed an increase in the frequency of perforin in CD8+ lymphocytes in HIV infected individuals immunized with a gp120-depleted HIV-1 immunogen while on antiviral drug therapy. Furthermore, the frequency of HIV-specific CD8+ perforin expressing cells correlated with the T helper immune response as measured by the lymphocyte proliferative response (LPR). The induction of such responses with immunization may have direct antiviral consequences and is being studied inm ongoing clinical trials.
Proliferating macrophages, dendritic cells, natural killer cells, T and B lymphocytes in the middle ear and Eustachian tube mucosa during experimental acute otitis media in the rat
Authors: Jecker P , Pabst R , Westermann J 
Published: March 2003

SummaryAlthough many studies focus on the increase of immunocompetent cells within the middle ear mucosa during acute otitis media it is poorly understood how this increase is mediated. The differentiation between two possible causes, i.e. immigration and local proliferation, would help to better understand the pathophysiology of this disease. Therefore, the number of proliferating macrophages, dendritic cells, natural killer cells and T and B lymphocytes was studied during acute otitis media in the rat middle ear mucosa (ME mucosa) and Eustachian tube mucosa (ET mucosa) by labelling proliferating leucocytes with the DNA precursor bromodeoxyuridine (BrdU). By removing the middle ear and Eustachian tube 24 h after BrdU injection, the contribution of immigrated newly formed cells was estimated. At this timepoint, many leucocytes in the ME and ET mucosa had incorporated BrdU (between 15 and 25% within the subsets). By analysing these tissues one hour after BrdU injection, the local proliferation rate was determined (between 2 and 9% within the subsets). Thus, the inflamed ME and ET mucosa are the destination of immunocompetent cells and, as our data show, the inflamed microenvironment supports local proliferation of immunocompetent cells.
Quantification of mucosal leucocyte endothelial cell interaction by in vivo fluorescence microscopy in experimental colitis in mice
Authors: Farkas S , Herfarth H , Rössle M , Schroeder J , Steinbauer M , Guba M , Beham A , Schölmerich J , Jauch K -W , Anthuber M 
Published: March 2003

Summary
Leucocyte recruitment to sites of intestinal inflammation is a crucial, multi-step process that leads ultimately to the accumulation of cells in the inflamed tissue. We established a new in vivo model system of experimental colitis to quantify leucocyte–endothelial cell interaction and leucocyte extravasation in the inflamed mucosa of the colon. Furthermore, we investigated the pathophysiological role of ICAM-1 in the intestinal microcirculation in vivo. Using the model of dextran sodium sulphate (DSS)-induced acute and chronic colitis in mice, in vivo microscopy was performed in the colonic submucosal postcapillary venules and the submucosal collecting venules in normal or inflamed murine colonic segments. ICAM-1 expression was blocked by an anti-ICAM-1 monoclonal antibody or by suppressing NF-κB activation by gliotoxin. Significant increases in leucocyte adhesiveness (51-fold in postcapillary venules, 30-fold in collecting venules, P &lt; 0·01) and extravasation (6·5-fold) could be demonstrated as early as day 2 of DSS-application in acute colitis (P &lt; 0·01). This was paralleled by increases in both the histological damage scores and myeloperoxidase activities. In chronic dextran sodium sulphate-induced colitis significant increases in leucocyte–endothelium interactions and leucocyte extravasation were observed. Blocking ICAM-1 expression with a monoclonal antibody or gliotoxin, leucocyte sticking and extravasation were significantly down-regulated in vivo compared to controls (&gt; 70%; P &lt; 0·01). This new model system offers the possibility to specifically assess the role of adhesion molecules in the colonic mucosa in vivo as well as to investigate and quantify the effectiveness of experimental therapeutic approaches in acute or chronic intestinal inflammation.
Increased numbers of circulating donor-specific T helper lymphocytes after human heart valve transplantation
Authors: Welters M J P , Oei F B S , Vaessen L M B , Stegmann A P A , Bogers A J J C , Weimar W 
Published: March 2003

SUMMARY
Implantation of cryopreserved human donor heart valves for either congenital or acquired cardiac disease has been performed since the last three decades. Although the clinical outcome is good, long-term valve degeneration resulting in dysfunction has been observed. A specific immunological response of the recipient against the allograft has been proposed as one of the factors involved in this process. Helper T lymphocytes play an important intermediate role in cellular and humoral immune response. Increasing numbers of circulating donor-specific helper T lymphocytes precursors (HTLp) correlate with graft rejection after organ transplantation. To investigate whether cryopreserved human donor heart valves are able to induce a donor-specific T helper response, we monitored the HTLp frequencies (HTLpf) in peripheral blood samples of 13 patients after valve allograft transplantation by use of a limiting dilution assay followed by an interleukin-2 bioassay. Prior to transplantation, HTLpf specific for donor and third-party antigens showed individual baseline levels. After allografting, the antidonor frequencies significantly increased in 11 of the 13 patients (P = 0·02). This was not found for stimulation with third-party spleen cells (P = 0·68), which indicates a donor-specific response. Maximal donor-specific HTLpf were already found at 1–2 months after operation. Valve allograft transplantation induces an increase in the numbers of donor-specific HTLp in peripheral blood of the patients. Analogous to organ transplantation, these HTLp may play a crucial role in events that lead to valve damage. Therefore, monitoring of HTLp in peripheral blood samples might be informative for donor valve degeneration (rejection) and subsequently valve allograft failure.
High frequency of circulating HBcAg-specific CD8 T cells in hepatitis B infection: a flow cytometric analysis
Authors: Matsumura S , Yamamoto K , Shimada N , Okano N , Okamoto R , Suzuki T , Hakoda T , Mizuno M , Higashi T , Tsuji T 
Published: March 2003

SUMMARYViral antigen-specific T cells are important for virus elimination. We studied the hepatitis B virus (HBV)-specific T cell response using flow cytometry. Three phases of HBV infection were studied: Group A, HBeAg (+) chronic hepatitis; Group B, HBeAb (+) HBV carrier after seroconversion; and Group C, HBsAb (+) phase. Peripheral T cells were incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analysed by flow cytometry. HBcAg-specific CD4 and CD8 T cells were identified in all three groups and the number of IFN-γ-positive T cells was greater than TNF-α-positive T cells. The frequency of IFN-γ-positive CD4 and CD8 T cells was highest in Group C, compared with Groups A and B. No significant difference in the HBcAg-specific T cell response was observed between Group A and Group B. The HBcAg-specific CD8 T cell response was diminished by CD4 depletion, addition of antibody against human leucocyte antigen (HLA) class I, class II or CD40L. Cytokine-positive CD8 T cells without HBcAg stimulation were present at a high frequency (7 of 13 cases) in Group B, but were rare in other groups. HBcAg-specific T cells can be detected at high frequency by a sensitive flow cytometric analysis, and these cells are important for controlling HBV replication.
Effects of granulocyte-macrophage colony stimulating factor (GM-CSF)in vivoon cytokine production and proliferation by spleen cells
Authors: Khatami S , Brummer E , Stevens D A 
Published: March 2003

SummaryGM-CSF is a potent stimulator of haematopoietic cells as well as some functions of granulocytes and macrophages. GM-CSF has many clinical uses; however, little is known about the effects of GM-CSF treatment in vivo on the responses of tissue lymphocytes in terms of secretion of Th-1 and Th-2 cytokines. We investigated this issue by measuring the responses of spleen cells from mice 24 h after treatment i.p. with saline or rmGM-CSF. GM-CSF at 16·7–50·0 µg/kg significantly increased (P &lt; 0·01) spleen cellularity 2–2·5-fold and enhanced proliferative responses of non-stimulated (no mitogen) as well as concanavalin A (Con A)-stimulated spleen cells. Secretion of IFN-γ by Con A (2·5 µg/ml)-stimulated spleen cells was significantly (P &lt; 0·01) increased from 1·8 µg/ml by control spleen cells to 5·2 μg/ml by GM-CSF spleen cells. IL-10 production was greater (0·25 μg/ml, P &lt; 0·05) by Con A-stimulated spleen cells from GM-CSF-treated mice compared to control spleen cells (0·06 μg/ml). By contrast, there were no significant differences in IL-4 production by Con A-stimulated spleen cells from the different groups. These results show that GM-CSF treatment increases spleen cellularity and primes lymphocytes for enhanced responses. The enhanced production of Th-1 cytokines by primed lymphocytes may partially explain the beneficial role of in vivo administration of GM-CSF in several clinical situations.
Immune complexes (IC) down-regulate the basal and interferon-γ-induced expression of MHC Class II on human monocytes
Authors: Barrionuevo P , Beigier-Bompadre M , De La Barrera S , Alves-Rosa M F , Fernandez G , Palermo M S , Isturiz M A 
Published: March 2003

SummaryThe interaction of Fc receptors for IgG (FcγRs) on monocytes/macrophages with immune complexes (IC) triggers regulatory and effector functions. Previous studies have shown that FcγR–IC interactions inhibit the IFN-γ-induced expression of MHC class II in murine macrophages. However, the mechanism(s) responsible for these effects have not been elucidated. In addition, whether this IC-dependent effect also occurs in human cells is not known. Taking into account the fact that IC and IFN-γ are frequently found in infections and autoimmune disorders, together with the crucial role MHC class II molecules play in the regulation of immune response, we explored the effect and mechanism of IC-induced MHC class II down-regulation in human peripheral blood mononuclear cells (PBMC). This effect was studied either in the presence or absence of IFN-γ. We demonstrate that IC exert a drastic inhibition of basal and IFN-γ-induced expression of MHC class II on human monocytes. This effect was mediated through the interaction of IC with both FcγRI and FcγRII. Moreover, similar results were obtained using supernatants from IC-treated PBMC. The IC-induced down-regulation of MHC class II is abrogated by pepstatin and phosphoramidon, supporting the role of aspartic protease(s) and metalloprotease(s) in this process. In parallel with MHC class II expression, antigen presentation was markedly inhibited in the presence of IC.
Antigen processing for MHC class I restricted presentation of exogenous influenza A virus nucleoprotein by B-lymphoblastoid cells
Authors: Voeten J T M , Rimmelzwaan G F , Nieuwkoop N J , Fouchier R A M , Osterhaus A D M E 
Published: March 2003

SummaryIn general, exogenous proteins are processed by antigen-presenting cells in the endosomes for major histocompatibility complex (MHC) class II presentation to CD4+ T cells, while proteins synthesized endogenously are processed in the cytoplasm for MHC class I presentation to CD8+ T cells. However, it is recognized that exogenous proteins can be processed for MHC class I presentation also, and evidence in favour of alternatives to the conventional MHC class I processing and presentation pathway is accumulating. Here, we show that exogenous recombinant influenza A virus nucleoprotein (rNP) is processed for MHC class I presentation to CD8+ cytotoxic T lymphocytes (CTL) by EBV-transformed, B-lymphoblastoid cell lines (B-LCL). Processing of rNP for HLA-B27-associated presentation seemed to follow the conventional MHC class I pathway predominantly, as presentation was diminished in the presence of lactacystin and brefeldin A, but was less sensitive to chloroquine and NH4Cl. HLA-B27-associated presentation was also observed using cells lacking a functional transporter associated with antigen processing, suggesting that alternative pathways may be exploited for processing of rNP.
Prevalence in myositis of antibodies recognizing anti-U3 RNA probably in a novel complex with 22/25 kD protein and not fibrillarin
Authors: Kubo M , Ihn H , Kuwana M , Yamane K , Yazawa N , Tamaki K 
Published: March 2003

SummaryNew antibodies against a U3 snRNP, which were named anti-Myo 22/25 antibodies, were detected in four (8%) of 53 serum samples from patients with polymyositis/dermatomyositis (PM/DM) by RNA immunoprecipitation. In the protein immunoprecipitation analysis, all four serum samples precipitated 22 kDa and 25 kDa proteins, which were not precipitated by normal serum or serum positive for antifibrillarin antibodies. Three of the four PM/DM patients had other identified autoantibodies including anti-PL-12 antibodies, antihistone antibodies (AHA), anti-SS-A antibodies and anti-SS-B antibodies defined by double immunodiffusion, ELISA or RNA immunoprecipitation, although there were no significant correlations between anti-Myo 22/25 antibodies and clinical or laboratory findings. There may be a subgroup of PM/DM patients whose sera are positive for anti-Myo 22/25 antibodies.
Endothelial targeting with C1-inhibitor reduces complement activationin vitroand duringex vivoreperfusion of pig liver
Authors: Bergamaschini L , Gobbo G , Gatti S , Caccamo L , Prato P , Maggioni M , Braidotti P , Di Stefano R , Fassati L R 
Published: March 2003

SummaryTissue damage during cold storage and reperfusion remains a major obstacle to wider use of transplantation. Vascular endothelial cells and complement activation are thought to be involved in the inflammatory reactions following reperfusion, so endothelial targeting of complement inhibitors is of great interest. Using an in vitro model of human umbilical vein endothelial cells (HUVEC) cold storage and an animal model of ex vivo liver reperfusion after cold ischaemia, we assessed the effect of C1-INH on cell functions and liver damage. We found that in vitro C1-INH bound to HUVEC in a manner depending on the duration of cold storage. Cell-bound C1-INH was functionally active since retained the ability to inhibit exogenous C1s. To assess the ability of cell-bound C1-INH to prevent complement activation during organ reperfusion, we added C1-INH to the preservation solution in an animal model of extracorporeal liver reperfusion. Ex vivo liver reperfusion after 8 h of cold ischaemia resulted in plasma C3 activation and reduction of total serum haemolytic activity, and at tissue level deposition of C3 associated with variable level of inflammatory cell infiltration and tissue damage. These findings were reduced when livers were stored in preservation solution containing C1-INH. Immunohistochemical analysis of C1-INH-treated livers showed immunoreactivity localized on the sinusoidal pole of the liver trabeculae, linked to sinusoidal endothelium, so it is likely that the protective effect was due to C1-INH retained by the livers. These results suggest that adding C1-INH to the preservation solution may be useful to reduce complement activation and tissue injury during the reperfusion of an ischaemic liver.
Graves’ disease is associated with an altered CXCR3 and CCR5 expression in thyroid-derived compared to peripheral blood lymphocytes
Authors: AUST G , SITTIG D , STEINERT M , LAMESCH P , LOHMANN T 
Published: March 2003

SUMMARYThe mechanisms by which T cells accumulate in the thyroid and support the autoimmune process in patients with Graves’ disease (GD) are poorly understood. Chemokines and their receptors may be involved in this process. We have analysed the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2 (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid-derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on PBL of GD patients (n = 16) did not differ from that of normal controls (n = 10). In GD, CXCR3+ (67·3 ± 4·0%versus 45·7 ± 2·1%) and CCR5+ T cells (42·5 ± 3·4%versus 18·8 ± 2·1%) showed a significant enrichment in the TL compared to PBL. The positive cells were contributed mainly by the CD4+CD45R0+ subset. TL are mostly primed CD45R0+ T cells, but surprisingly, they had significantly higher levels of CXCR4+ cells among TL (96·2 ± 1·0%) compared to PBL (66·8 ± 4·2%). However, CXCR4 has been induced during in vitro isolation of TL. There was no correlation between chemokine receptors and the level of TSH-receptor and thyroid peroxidase autoantibodies. CCR3+ and CCR2+ cells remained unchanged in TL compared to PBL. We could confirm the results using RT PCR and immunohistology. In summary, TL showed a different chemokine receptor pattern compared to PBL from the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of T cells to the thyroid in GD.
The strength of B cell immunity in female rhesus macaques is controlled by CD8+T cells under the influence of ovarian steroid hormones
Authors: LÜ F X , ABEL K , MA Z , ROURKE T , LU D , TORTEN J , MCCHESNEY M , MILLER C J 
Published: March 2003

SUMMARYTo understand more clearly how mucosal and systemic immunity is regulated by ovarian steroid hormones during the menstrual cycle, we evaluated the frequency of immunoglobulin- and antibody-secreting cells (ISC, AbSC) in genital tract and systemic lymphoid tissues of normal cycling female rhesus macaques. The frequency of ISC and AbSC was significantly higher in tissues collected from animals in the periovulatory period of the menstrual cycle than in tissues collected from animals at other stages of the cycle. The observed changes were not due to changes in the relative frequency of lymphocyte subsets and B cells in tssues, as these did not change during the menstrual cycle. In vitro, progesterone had a dose-dependent inhibitory effect, and oestrogen had a dose-dependent stimulatory effect on the frequency of ISC in peripheral blood mononuclear cell (PBMC) cultures. The in vitro effect of progesterone and oestrogen on ISC frequency could not be produced by incubating enriched B cells alone with hormone, but required the presence of CD8+ T cells. Following oestrogen stimulation, a CD8+ enriched cell population expressed high levels of IFN-gamma and IL-12. The changes in B cell Ig secretory activity that we document in the tissues of female rhesus macaques during the menstrual cycle is due apparently to the action of ovarian steroid hormones on CD8+ T cells. Thus, CD8+ T cells control B cell secretory activity in both mucosal and systemic immune compartments. Understanding, and eventually manipulating, the CD8+ regulatory cell–B cell interactions in females may produce novel therapeutic approaches for autoimmune diseases and new vaccine strategies to prevent sexually transmitted diseases.
Leptin inhibits stress-induced apoptosis of T lymphocytes
Authors: FUJITA Y , MURAKAMI M , OGAWA Y , MASUZAKI H , TANAKA M , OZAKI S , NAKAO K , MIMORI T 
Published: March 2003

SUMMARYLeptin, which is secreted by adipocytes, the placenta and the stomach, not only controls appetite through leptin receptors in the hypothalamus but also regulates cell-mediated immunity. In this study we have demonstrated that continuous injection of leptin prevents the reduction in lymphocyte numbers normally observed in fasted and steroid-injected mice. Consistent with leptin-induced protection, we observed up-regulation of the bcl-xL gene as a result of signal transduction via leptin receptors on lymphocytes. We suggest that leptin might contribute to the recovery of immune suppression in malnourished mice by inhibiting lymphocyte apoptosis.
Circulating immunoglobulin-bound transforming growth factorβat a late tumour-bearing stage impairs antigen-specific responses of CD4+T cells
Authors: HARADA M , TATSUGAMI K , NOMOTO M , NOMOTO K 
Published: March 2003

SUMMARYIn order to elucidate the mechanisms by which tumour-specific CD4+ T- cell responses are impaired during tumour development, an attempt was made to identify factors which impair CD4+ T-cell responses at a late tumour-bearing stage. Plasma from mice bearing B16 melanoma for 30 days (plasma d30) showed a more profound immunosuppressive effect on the in vitro proliferation of unrelated antigen-specific CD4+ T cells in the presence of both antigen and antigen-presenting cells (APC) than plasma from naïve mice. The level of plasma transforming growth factor (TGF)-β was elevated in mice bearing B16 melanoma for 30 days compared with naïve mice, and the suppressive effect of plasma d30 was partially diminished by the neutralization of TGF-β. Interestingly, immunoglobulin (IgG)-bound TGF-β, but not IgG-unbound TGF-β, in plasma d30 was suggested to be responsible for the immunosuppressive activity. In addition, no suppressive effect of plasma d30 was observed when antigen was added as a class II peptide, thus suggesting that the impaired proliferation of CD4+ T cells in the presence of plasma d30 was due to a dysfunction of antigen uptake/processing by APC. Furthermore, dissociation between IgG and TGF-β resulted in a loss of the suppressive activity of plasma d30. Taken together, these results suggest that circulating IgG-bound TGF-β is, at least in part, responsible for the impaired responses of CD4+ T cells at the late tumour-bearing stage by suppressing antigen uptake/ processing by APC.
Longitudinal analysis of the T-cell receptor (TCR)-VA and -VB repertoire in CD8+T cells from individuals immunized with recombinant hepatitis B surface antigen
Authors: HÖHN H , NEUKIRCH C , FREITAG K , NECKER A , HITZLER W , SELIGER B , MAEURER M J 
Published: March 2003

SUMMARYRecent studies have suggested that vaccination induces alterations in the T cell receptor (TCR) repertoire. We investigate the diversity of the TCR repertoire after immunization with a recombinant hepatitis B surface vaccine in seven healthy subjects in CD8+ T cells in peripheral blood lymphocytes. Cellular immune responses were monitored over time by sorting CD8 T cells followed by TCR-VA and -VB complementarity determining region 3 (CDR3) analysis. Frequency of individual VB families was determined by flow cytometry. TCR-VA/VB repertoires obtained from CD8+ T cells drawn after vaccination were compared to the TCR repertoire determined prior to vaccination. Monoclonal TCR transcripts could be detected exclusively in CD8+, but not in CD4+ T cells. Such monoclonal TCR transcripts were either stable in some individuals, or could only be detected at certain time points after vaccination. Sorting of monoclonal TCR-VB3+ T cells, which constituted up to 5% of the CD8+ T cell population from one individual, revealed that this T cell clone recognizes an epitope provided by the recombinant hepatitis B vaccine presented by MHC-class I on autologous antigen-presenting cells. Examination of the structural anatomy, defined by the TCR, and the frequency of T cells responding to the immunizing antigen may be helpful to provide surrogate markers to monitor cellular immune responses induced by protein antigens utilized for vaccination.