bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of DNA immunization against mycobacterial infection is associated with the early emergence of interferon-gamma (IFN-γ)-secreting lymphocytes
Authors: Kamath A T , Groat N L , Bean A G D , Britton W J 
Published: March 2003

SUMMARYThe development of more effective anti-tuberculosis (TB) vaccines would contribute to the global control of TB. Understanding the activated/memory T cell response to mycobacterial infection and identifying immunological correlates of protective immunity will facilitate the design and assessment of new candidate vaccines. Therefore, we investigated the kinetics of the CD4+ T cell response and IFN-γ production in an intravenous challenge model of Mycobacterium bovis bacille Calmette–Guérin (BCG) before and after DNA immunization. Activated/memory CD4+ T cells, defined as CD44hiCD45RBlo, expanded following infection, peaking at 3–4 weeks, and decreased as the bacterial load fell. Activated/memory CD4+ T cells were the major source of IFN-γ and the level of antigen-specific IFN-γ-secreting lymphocytes, detected by ELISPOT, paralleled the changes in bacterial load. To examine the effects of a DNA vaccine, we immunized mice with a plasmid expressing the mycobacterial secreted antigen 85B (Ag85B). This led to a significant reduction in mycobacteria in the liver, spleen and lung. This protective effect was associated with the rapid emergence of antigen-specific IFN-γ-secreting lymphocytes which were detected earlier, at day 4, and at higher levels than in infected animals immunized with a control vector. This early and increased response of IFN-γ-secreting T cells may serve as a correlate of protective immunity for anti-TB vaccines.
Human T cells with a type-2 cytokine profile are resistant to apoptosis induced by primary activation: consequences for immunopathogenesis
Authors: Carbonari M , Tedesco T , Del Porto P , Paganelli R , Fiorilli M 
Published: March 2003

SUMMARYThe mechanisms leading to a relative dominance of T cells producing type 2 cytokines in certain human immune disorders are still unclear. We investigated the relative susceptibility to apoptosis induced by primary in vitro activation of human type 1 (producing interferon-gamma (IFN-γ)) or type 2 (producing IL-4) T cells. Peripheral blood lymphocytes were isolated from patients with immune disorders characterized by expansion of type 2 cells (four with AIDS and hyper-IgE/hypereosinophilia, one with Churg–Strauss syndrome, and one with idiopathic hypereosinophilic syndrome) or from individuals with normal cytokine balances. Cells were stimulated for 16 h with ionomycin and phorbol ester, and apoptosis of cytokine-producing cells was assessed by flow cytometry. T cells with a type-2 cytokine profile, i.e. producing IL-4 alone, were significantly more resistant to activation-induced apoptosis than those producing IFN-γ alone. This was observed in AIDS patients, whose type 2 cells were mostly CD8+, as well as in the patients with Churg–Strauss and with hypereosinophilic syndrome. CD4+ and CD8+ IL-4-producing cells were equally resistant to apoptosis. Lower susceptibility to apoptosis of type-2 T cells was also observed in subjects with normal cytokine balances. Bcl-2 expression was high in type-2 cells and in viable type-1 cells, whereas it was low in apoptotic type-1 cells. Resistance to activation-induced apoptosis may explain the expansion of cells producing type-2 cytokines in certain immune disorders.
Differential effect of cholera toxin on CD45RA+ and CD45RO+ T cells: specific inhibition of cytokine production but not proliferation of human naive T cells
Authors: Eriksson K , Nordström I , Czerkinsky C , Holmgren J 
Published: March 2003

SUMMARYWe have studied how cholera toxin (CT) and its non-toxic cell-binding B-subunit (CTB) affect the activation of pure human T cells in an anti-CD3-driven system. CT, as opposed to CTB, strongly suppressed the proliferative responses as well as cytokine production in CD4+ and CD8+ T cells. CT however, had a differential effect on naive and activated/memory T cell subsets. Costimulation through exogenous IL-2 or through CD28 cross-linking rescued the proliferation of CT-treated naive CD45RA+ T cells, but not of activated/memory CD45RO+ cells. IL-2 production and IL-2 receptor expression were markedly reduced by CT in all T cell fractions, i.e. also in CD45RA+ cells which had maintained proliferative responses. However, the proliferative responses of CT-treated CD45RA+ T cells were IL-2-dependent, as shown by blocking experiments using anti-IL-2 antibodies. These results indicate (i) that CTB has no cytostatic effect on human T cells, (ii) that CT affects proliferation and cytokine production by two different signal pathways, and (iii) that CT might interact with a signal pathway generated through or influenced by CD45.
The 75-kD tumour necrosis factor (TNF) receptor is specificallyup-regulated in monocytes during Q fever endocarditis
Authors: Ghigo E , Capo C , Amirayan N , Raoult D , Mege J-L 
Published: March 2003

SUMMARYQ fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular microorganism that inhabits monocytes/macrophages. The dysregulated production of TNF-α in Q fever endocarditis has been associated with defective killing of C. burnetii by patient monocytes. As soluble receptors for TNF-α (TNF-R55 and TNF-R75) regulate TNF-α activity, we investigated their release by monocytes in Q fever. Spontaneous and C. burnetii-stimulated release of TNF-R75, but not of TNF-R55, was up-regulated in patients with ongoing endocarditis compared with controls. The increase in TNF-R75 release was related to the activity of Q fever endocarditis, since TNF-R75 release was similar in patients with cured endocarditis and controls. While spontaneous release of TNF-R75 by monocytes from patients with ongoing Q fever endocarditis occurred without changes in its membrane expression, C. burnetii increased the surface expression of TNF-R75. In addition, TNF-R75 transcripts were increased in resting and C. burnetii-stimulated monocytes from patients with ongoing endocarditis. On the other hand, TNF-R75 release was not related to TNF-α secretion. These results indicate that the modulation of TNF-R75 is a critical feature of the pathophysiology of Q fever endocarditis.
Induction of CD95 ligand expression on T lymphocytes and B lymphocytes and its contribution to apoptosis of CD95-up-regulated CD4+ T lymphocytes in macaques by infection with a pathogenic simian/human immunodeficiency virus
Authors: Sasaki Y , Ami Y , Nakasone T , Shinohara K , Takahashi E , Ando S , Someya K , Suzaki Y , Honda M 
Published: March 2003

SUMMARYUsing an established SIV/HIV-C2/1-infected cynomolgus monkey model displaying stable CD4+ T cell depletion, the kinetics of apoptosis and the levels of expression of CD95 membrane-associated CD95L on lymphocytes were investigated to test the involvement of the CD95/CD95L system in CD4+ T lymphocyte loss in vivo. Rapid depletion of CD4+ T cells occurred up to 2 weeks after infection, with chronic CD4+ T lymphopenia thereafter. During the initial CD4+ T cell loss, which was accompanied by viraemia, about 90% of the peripheral CD4+ T cell subset underwent spontaneous apoptotic cell death during 24 h of culture. Increased expression of CD95 was observed on both CD4+ and CD8+ T cell subsets, with CD95 expression on CD8+ cells declining rapidly, but high CD95 expression being maintained on CD4+ cells. Since CD95L was expressed on CD8+ T cells, B cells and to a lesser extent on CD4+ T cells, this suggests that CD95-mediated apoptosis might be controlled in an autocrine/paracrine fashion.
Autoimmunity in ulcerative colitis (UC): a predominant colonic mucosal B cell response against human tropomyosin isoform 5
Authors: Onuma E K , Amenta P S , Ramaswamy K , Lin J J-C , Das K M 
Published: March 2003

SUMMARYWe set out to examine if the IgG-producing cells in the colonic mucosa in UC are committed to tropomyosin isoform 5 (hTM5), a putative autoantigen in UC. Lamina propria mononuclear cells (LPMC) were isolated from colonoscopic biopsy specimens from recto-sigmoid and proximal colon. Twenty-three patients with UC, eight with Crohn's colitis (CC), and 10 non-inflammatory bowel disease (non-IBD) controls were included. The ELISPOT assays were used to quantify lamina propria B cells producing total immunoglobulin (IgA, IgG, IgM), IgG, IgA, as well as IgG against hTM5 isoform. The median value of percentage of total IgG-producing lymphocytes was similar in UC (12%) and CC (11%), but was significantly (P &lt; 0·0002) higher than non-IBD controls (6%). However, in UC, but not in CC and non-IBD, a large number of lamina propria B cells produced IgG against hTM5 (median values: UC 42%, CC 2·5%, non-IBD 0%). This difference in UC when compared with CC and non-IBD was highly significant (P &lt; 0·00001). Twenty-one of 23 (91%) patients with UC had percentage of anti-hTM5 IgG-producing immunocytes more than 2 s.d. above the mean for non-UC patients. In UC but not in CC and non-IBD controls, the increased number of IgG-producing cells are largely committed to produce IgG against hTM5-related epitope(s).
Thalidomide analogue CC-3052 reduces HIV+ neutrophil apoptosisin vitro
Authors: Guckian M , Dransfield I , Hay P , Dalgleish A G 
Published: March 2003

SUMMARYThalidomide has significant immunomodulatory properties and has been used successfully in the treatment of oral ulcers and wasting in HIV patients. However, its use is limited by its poor bioavailability due to low solubility and short half life in solution, and teratogenic and neurotoxic side-effects. Recently, water-soluble analogues of thalidomide with significantly greater immunomodulatory activity and reduced side-effects have become available. We examined the effect of thalidomide and one analogue, CC-3052, on neutrophil apoptosis following culture for 20 h in vitro. Apoptosis was assessed by reduced CD16 expression and Annexin V binding using flow cytometry. Thalidomide or CC-3052 alone had no effect on neutrophil apoptosis when used at physiological levels. However, when used together with prostaglandin E2 (10−7 m), a potent adenylate cyclase activator, CC-3052 but not thalidomide (both 10−5 m) reduced apoptosis in neutrophils from normal and HIV+ donors. The reduced apoptosis could not be attributed to the ability of CC-3052 to reduce tumour necrosis factor-alpha (TNF-α) production, but may be due to its PDE4 inhibitor properties, as it increased [cAMP]i, and mimicked the effect of increasing [cAMP]i using dibutryl cAMP, a membrane-permeable analogue of cAMP. The results suggest a role for thalidomide analogue CC-3052 in reducing persistent activation of the TNF-α system in HIV without markedly impairing neutrophil viability.
The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema
Authors: Orteu C H , Rustin M H A , O'toole E , Sabin C , Salmon M , Poulter L W , Akbar A N 
Published: March 2003

SUMMARYAtopic eczema (AE) is characterized by the persistence of infiltrating T lymphocytes in the dermis. To test the hypothesis that dysregulation of normal T cell apoptosis may contribute to the pathogenesis and chronicity of AE we compared patients with a normal resolving immune response (Mantoux reaction (MR)) induced in healthy volunteers by cutaneous PPD injection. Significantly less T cell apoptosis was observed in lesional skin of AE patients compared with either the peak or the resolution phase of the MR (P &lt; 0·0001). The low incidence of T cell apoptosis in AE was associated with significantly increased levels of Bcl-2 relative to Bax (P &lt; 0·0001) and significantly decreased CD95-L expression (P &lt; 0·002) compared with the resolving MR. The cytokines IL-15 and interferon-beta (IFN-β), which prevent activated T cell apoptosis, were expressed maximally on day 7 and day 14 of the MR, respectively. In contrast, AE patients expressed high levels of both IL-15 and IFN-β in cutaneous lesions at the same time. This suggests that the co-expression of two anti-apoptotic cytokines, which are not found together during resolving cutaneous responses, may contribute to excessive T cell survival which leads to the persistence of inflammation in patients with AE.
Intrapulmonary concentrations of inflammatory cytokines in a mouse model of chronic respiratory infection caused byPseudomonas aeruginosa
Authors: Yanagihara K , Tomono K , Kuroki M , Kaneko Y , Sawai T , Ohno H , Miyazaki Y , Higashiyama Y , Maesaki S , Kadota J-I , Kohno S 
Published: March 2003

SUMMARYWe investigated the role of inflammatory cytokines in a mouse model of chronic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and determined the effects of clarithromycin therapy on the production of these cytokines. The concentrations of IL-1β, IL-2, IL-4, IL-5, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) were measured serially in the lungs of mice with experimentally induced chronic respiratory P. aeruginosa infection until 60 days after inoculation. The concentrations of these cytokines during the course of the disease were significantly higher than baseline (before inoculation, P &lt; 0.01 for all cytokines). Clarithromycin significantly inhibited the production of IL-1β and TNF-α in the lung (P &lt; 0.01). The same treatment also reduced the levels of other cytokines, albeit insignificantly. Treatment with anti-TNF-α antibody significantly reduced the number of pulmonary lymphocytes and concentration of IL-1β in the lung (P &lt; 0.01), but did not change the number of viable bacteria. Our findings resemble those detected in bronchoalveolar lavage fluid of patients with DPB and indicate that inflammatory cytokines play an important role in chronic P. aeruginosa lung infection. Our results also show that macrolides modulated the production of these cytokines, ultimately reducing lymphocyte accumulation in the lung. Our data suggest that anti-TNF-α antibody might be a useful new strategy for the treatment of chronic respiratory P. aeruginosa infection.
Apoptosis and apoptosis-associated perturbations of peripheral blood lymphocytes during HIV infection: comparison between AIDS patients and asymptomatic long-term non-progressors
Authors: Moretti S , Marcellini S , Boschini A , Famularo G , Santini G , Alesse E , Steinberg S M , Cifone M G , Kroemer G , De Simone C 
Published: March 2003

SUMMARYThis study was designed to compare the degree of lymphocyte apoptosis and Fas–Fas ligand (FasL) expression in AIDS patients and long-term non-progressors (LTNPs) and correlate these parameters with apoptosis-associated perturbations in lymphocyte function. LTNPs had a lower frequency of apoptotic CD4+ and CD8+ T cells compared with subjects with AIDS. This correlated with a lower frequency of cells expressing Fas and FasL. The frequency of selected lymphocyte populations exhibiting a disrupted mitochondrial transmembrane potential (ΔΨm) and increased superoxide generation was lower in LTNPs than in patients with AIDS; these abnormalities were associated with lower levels of caspase-1 activation in LTNPs. The results indicate a significantly reduced level of apoptosis and apoptosis-associated parameters in LTNPs than in patients developing AIDS. Based on these findings, a crucial role for mitochondria can be predicted in the process of lymphocyte apoptosis during the evolution of AIDS.
Reduced expression of the complement receptor type 2 (CR2, CD21) by synovial fluid B and T lymphocytes
Authors: Illges H , Braun M , Peter H H , Melchers I 
Published: March 2003

SUMMARYThe expression of CR2 (CD21) by synovial B and T lymphocytes of patients suffering from various forms of arthritis was analysed with cytofluorometry and with reverse transcriptase-polymerase chain reaction. CR2 (CD21) cell surface protein was detected in normal quantities on peripheral B cells, but was almost absent on synovial B lymphocytes of the same patients. This reduction was most severe in patients with rheumatoid arthritis, but also observed in all other cases. CR2 (CD21) did not reappear after in vitro culture. CR2 (CD21) mRNA was also strongly reduced in synovial B and T lymphocytes. Synovial fluid B lymphocytes were larger than peripheral blood B lymphocytes, while T cells from the same patients showed no size differences. We conclude that synovial fluid B lymphocytes have undergone an irreversible step towards terminal differentiation. The presence or absence of CR2 (CD21) mRNA in peripheral versus synovial T cells indicates that CR2 (CD21) is also differentially expressed by T lymphocytes.
Roles of tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and IL-10 in the modulation of intercellular adhesion molecule-1 (ICAM-1) expression by macrophages during mycobacterial infection
Authors: Tomioka H , Shimizu T , Maw W W , Ogasawara K 
Published: March 2003

SUMMARYProfiles of ICAM-1 expression on cultured murine peritoneal macrophages infected with Mycobacterium avium complex (MAC) were examined, with special reference to modulating roles of TNF-α, TGF-β, and IL-10. When macrophages were infected with MAC, ICAM-1 expression, measured by microscopic counting of ICAM-1+ macrophages stained with anti-ICAM-1 antibody, ELISA, and flow cytometric analysis, was rapidly increased, peaking at day 3 (early-phase up-regulation) due to endogenous TNF-α, and thereafter gradually declined to the normal level within 1 week or more (late-phase down-regulation). The late-phase ICAM-1 down-regulation was also seen in macrophages phagocytosing heat-killed MAC and those stimulated with lipopolysaccharide but not in macrophages phagocytosing latex beads. ICAM-1 mRNA expression was augmented markedly at day 1 after MAC infection and thereafter decreased. While TNF-α and IL-10 production by MAC-infected macrophages was observed during the first 3 days, TGF-β production was initiated from day 3 and continued until day 14. Exogenously added TGF-β strongly inhibited the early-phase increase in ICAM-1 expression by infected macrophages, and the blockade of endogenous TGF-β with anti-TGF-β antibody markedly inhibited late-phase ICAM-1 down-regulation. Moderate blocking effect was also observed for anti-IL-10 antibody. On the other hand, late-phase ICAM-1 down-regulation was not prevented by the addition of exogenous TNF-α. Therefore, TGF-β and IL-10, especially the former, appear to play active roles in the late-phase down-regulation of ICAM-1 in MAC-infected macrophages during long-term cultivation.
Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes
Authors: Nishioji K , Okanoue T , Itoh Y , Narumi S , Sakamoto M , Nakamura H , Morita A , Kashima K 
Published: March 2003

SUMMARYTo clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P &lt; 0·02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P &lt; 0·05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.
Failure to detect HLA-A*6802-restricted CD8+ T cells specific forChlamydia trachomatisantigens in subjects from trachoma-endemic communities
Authors: Mahdi O S M , Whittle H C , Joof H , Mabey D C W , Bailey R L 
Published: March 2003

SUMMARYThe role of HLA-A*6802-restricted CD8+ T cells in chlamydial disease was investigated in human ocular infections. Peptides with predicted binding motifs for HLA-A*6802 were synthesized using sequences based on chlamydial antigens, major outer membrane protein (MOMP), macrophage infectivity potentiator (MIP) and heat shock protein (hsp70). Peptides were pooled according to Chlamydia trachomatis protein type and serovar, and were tested in 51Cr-release cytotoxic T lymphocyte (CTL) and enzyme-linked immunospot (ELISPOT) assays, using peripheral blood mononuclear cells (PBMC) isolated from subjects living in trachoma-endemic communities in The Gambia. Significant CTL activity or interferon-gamma release was not detected in any of the subjects, suggesting either that HLA-A*6802 CD8+ T cells may not be important in ocular infections or that the peptides chosen did not represent epitopes.
Prevention of murine acute graft-versus-host disease by staphylococcalenterotoxin B treatment
Authors: Takenaka K , Fujiyama Y , Andoh A , Sasaki T , Amakata Y , Matsubara H , Hodohara K , Bamba T 
Published: March 2003

SUMMARYRetroviral superantigens such as minor lymphocyte stimulating (Mls) antigen play an important role in the pathogenesis of acute graft-versus-host disease (GVHD). However, it remains unclear how exogenous bacterial superantigens modulate acute GVHD. In this study, we tested the effects of staphylococcal enterotoxin B (SEB) on the development of acute GVHD in a model involving the systemic transfer of parental C57Bl/6 spleen cells into BDF1 mice. SEB treatment suppressed the expansion of donor-derived T cells and blocked the decrease in the number of host cells. Impaired haematopoiesis was actually rescued by treatment with SEB. In SEB-treated mice, both spontaneous proliferation and IL-2 production in T cells were suppressed on day 2 after parental cell infusion. On day 21, the number of donor-derived CD4+ Vβ8+ T cells markedly decreased in the spleen of SEB-treated mice. Donor-derived CD4+ T cells failed to proliferate in response to host alloantigens, and both donor- and host-derived T cells were unable to produce IL-2 in response to concanavalin A stimulation, suggesting that SEB treatment induced a general immunosuppressive state. Our results indicate that SEB treatment prevents the development of acute GVHD by leading to unresponsiveness of donor-derived T cells against host alloantigens in a Vβ-restricted and unrestricted manner.