bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferation of distinct human T cell subsets in response to live, killed or soluble extracts of Mycobacterium tuberculosis and Myco. avium
Authors: Esin S , Batoni G , Källenius G , Gaines H , Campa M , Svenson S B , Andersson R , Wigzell H 
Published: November 2003

SUMMARY
The proliferative responses of distinct cell subsets from healthy, bacille Calmette–Guérin (BCG)-vaccinated blood donors were assessed after in vitro stimulation with live or UV-killed Mycobacterium tuberculosis and Myco. avium or with soluble extracts obtained from either mycobacterial species. Proliferation of cell subsets was evaluated by flow cytometric determination of 5-bromo-2′-deoxy-uridine incorporation into DNA and simultaneous identification of surface phenotypic markers. In the presence of monocytes, the response to whole (live or killed) bacteria was characterized by a predominant proliferation of CD4+αβ+ T cells and, to a lesser extent, of CD8+αβ+ T cells. Proliferation of CD8+αβ+ T cells was primarily elicited by live rather than killed bacilli (P &lt; 0.05). Conversely, when soluble bacterial extracts were used as stimulators, a preferential proliferation of γδ+ T cells, expressing predominantly Vγ9+ and Vδ2+ T cell receptor chains, was recorded. Moreover, when monocyte-depleted cell populations were directly cultured with live bacteria, a marked proportion of CD3–CD16+ (natural killer (NK)) cells was detected among the responding cells. Although both αβ, γδ and NK cells have been previously shown to react with mycobacteria in vitro, their relative contributions to the response have been difficult to assess. Using a flow cytometric technique which allows direct identification of proliferating cells within complex cell populations, our study demonstrates significant differences in the ability of various mycobacterial antigen preparations to elicit proliferation of distinct cell subsets.
Selective CD4+ T cell deletion after specific activation in HIV-infected individuals; protection by anti-CD28 monoclonal antibodies
Authors: Cottrez F , Capron A , Groux H 
Published: November 2003

Abstract
AIDS is characterized by a progressive decline in the number of CD4+ T cells. This is preceded by an early selective defect in the proliferation of these cells to recall antigens [1–3], pokeweed mitogen (PWM) [4–6] and to superantigens (SAg) [4,7]. In contrast, the proliferative response to phytohaemagglutinin (PHA) remains intact [1,2,5]. We and others have shown that the proliferative defect in response to some stimuli was in fact due to the induction of cell death [4,7]. The activation-induced cell death mechanism that explains the proliferative defects observed in vitro might also account for the progressive in vivo deletion of CD4+ T cells. Indeed, studies performed on different models of primates have shown that induction of cell death in CD4+ T cells was detected only when T cells were isolated from animals infected with a type of retrovirus that induces an AIDS-like disease [8]. This correlation prompted us to analyse further the mechanism of HIV-induced activation cell death to determine the specificity and rate of induction of cell death. T cells from HIV-infected individuals were activated with superantigens and the Vβ T cell receptor (TCR) expression analysed. Data presented here show that cell death is restricted to activated CD4+ T cells, and does not affect bystander cells. More importantly, addition of anti-CD28 MoAb specifically inhibited the induction of apoptosis, raising possibilities for therapy.
Soluble products of inflammatory reactions are not induced in children with asymptomatic Plasmodium falciparum infections
Authors: Jakobsen P H , Mckay V , N'Jie R , Olaleye B O , D'Alessandro U , Bendtzen K , Schousboe I , Greenwood B M 
Published: November 2003

Abstract
A proportion of children with Plasmodium falciparum infection have a high parasitaemia without accompanying fever, indicative of different clinical thresholds of parasitaemia. Higher levels of IL-10, IL-1Ra and sIL-4R but not sIL-2R were found in children with P. falciparum malaria, compared with levels in children with asymptomatic P. falciparum infections and in healthy children. Concentrations of IL-10 and IL-1Ra were correlated with levels of parasitaemia, but the association of cytokine levels with disease was independent of the association with parasitaemia. Children may tolerate a high parasitaemia by neutralizing the parasite-derived toxins. When studying potential anti-toxic molecules we found that children with symptomatic infections had lower concentrations of a phospholipid-binding molecule, β2-glycoprotein I (β2-GPI), compared with children with asymptomatic infections or healthy children. In conclusion, cytokines were found in much higher concentrations in children with symptomatic P. falciparum malaria than in children with asymptomatic infections, whilst the former had lower concentrations of β2-GPI.
Peptide immunization in humans: a combined CD8+/CD4+ T cell-targeted vaccine restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes (CTL)
Authors: Brander C , Corradin G , Hasler T , Pichler W J 
Published: November 2003

Abstract
Immunization with short antigenic peptides represents a potential strategy to induce peptide-specific CTL in vivo. In this study, a synthetic vaccine consisting of an HIV-derived, HLA-A2.1-binding CTL epitope and a tetanus toxin-derived T helper epitope was evaluated for its capacity to induce peptide-specific CTL in humans. Thirteen volunteers were immunized and boosted twice with 100 μg of the CTL epitope plus 300 μg of the T helper peptide (p30). Peripheral blood mononuclear cells (PBMC) were regularly analysed for cytotoxic and proliferative responses before, between and after the immunizations, and the serum was tested for anti-peptide antibodies. No unequivocal induction of HIV peptide-specific CTL in any of the volunteers was observed. However, a wide pattern of mild and transient side reactions was observed, ranging from local redness at the injection site to generalized exanthema, myalgias, arthralgias and fever. The side-effects were related to the T helper epitope, as they were similar to the side-effects experienced after tetanus immunization, correlated to the magnitude of the p30-specific in vitro proliferative response, and occurred only if p30 was co-injected. No antibodies against the HIV-derived peptides nor against p30 were detectable in the serum after repeated immunizations. The data suggest that the CTL peptide, at the concentration used in this study, failed to induce a cytotoxic immune response in vivoalthough the T helper peptide seems to be capable of restimulating the specific memory T cells.
In vitro activation of antigen-presenting cells (APC) by defined composition of Quillaja saponaria Molina triterpenoids
Authors: Behboudi S , Morein B , Villacres-Eriksson M 
Published: November 2003

Abstract
The capacity of adjuvants to stimulate cytokine production by APC is important for the initiation of the immune response. Novel adjuvant formulations based on the iscom technology have been developed using selected triterpenoid components from Quillaja saponaria Molina. Five of these new Quillaja formulations were used to prepare matrix (an antigen-free particle) and tested for their capacity to stimulate IL-1 secretion by murine peritoneal cells in vitro. The formulation denominated QH 7.0.3 was superior to the other matrix formulations, including the original spikoside matrix. The QH 7.0.3 formulation in iscoms containing influenza virus envelope antigens induced IL-1 secretion more efficiently than the antigen-free matrix, or a mixture of matrix and viral antigens, or the free Quillaja components of similar composition. Compared with adjuvants known as IL-1 inducers, QH 7.0.3 flu-iscoms were as efficient as the most prominent IL-1 inducer, i.e. lipopolysaccaride (LPS) and superior to cholera toxin (CT) and muramyl dipeptide (MDP). These results indicate that the composition per se of triterpenoids included in iscoms or matrix has a prominent influence on the level of APC activation which may result in qualitatively different immune responses in vivo
Analysis of Vκ genes in rheumatoid arthritis (RA) synovial B lymphocytes provides evidence for both polyclonal activation and antigen-driven selection
Authors: Moyes S P , Brown C M , Scott B B , Maini R N , Mageed R A 
Published: November 2003

Abstract
To define mechanisms of sustained activation of synovial B lymphocytes in RA, we studied hybridomas established from the local synovial B cell repertoire of two RA patients for Vκ gene expression and for antigen-binding specificity. The analyses revealed that members of the main Vκ families (I, II and III) were utilized at frequencies consistent with random Vκ gene family use. Furthermore, although the hybridomas expressed genes frequently seen in response to other self- and exogenous antigens, only one VκI- and two of three VκIII-expressing hybridomas exhibited reactivity with self-antigens. Nucleotide sequence analysis revealed that all hybridomas, with the exception of rheumatoid factor (RF)-producing hybridomas, expressed Vκ genes highly related to known germ-line genes (99.3–100% homology) and that diversity was generated by deletions and random nucleotide insertions at the Vκ–Jκ junction. Examination of the few nucleotide changes seen within the Vκ genes revealed a predominance of silent to replacement changes. Moreover, most of these changes can be attributable either to allotypic variations or to limited random nucleotide replacements independent of antigen selection. In contrast, one IgG-RF (B4D8) exhibited predominantly replacement nucleotide changes in the complementarity-determining regions, suggestive of antigen-driven selection. The random expression of immunoglobulin variable region genes with no, or little, evidence of mutation in the synovial B lymphocyte repertoire, including natural polyreactive antibodies, alongside mutated IgG-RF, suggest that both polyclonal activation and antigen-driven responses occur in RA synovia.
Activation of epitope-specific memory cytotoxic T lymphocyte responses by synthetic peptides
Authors: Reali E , Guerrini R , Giori B , Borghi M , Marastoni M , Tomatis R , Traniello S , Masucci M G , Gavioli R 
Published: November 2003

Abstract
Cytotoxic T lymphocytes (CTL) recognize antigens as short peptides selected for presentation by their ability to bind to MHC class I molecules. Polyclonal Epstein–Barr virus (EBV)-specific memory CTL responses, reactivated from blood lymphocytes of HLA-A11-positive individuals by stimulation with the autologous EBV-transformed lymphoblastoid cell line (LCL), are often dominated by reactivities directed to the peptide epitope IVTDFSVIK (IVT), corresponding to amino acids 416–424 of EBV nuclear antigen-4 (EBNA4). We now report the selective activation of IVT-specific CTL by stimulation of lymphocytes with the corresponding synthetic peptide. A more than 10-fold increase in frequency of CTL clones with this specificity (from 8% to 96%) was obtained when the peptide was presented by HLA-A11-transfected T2 cells (T2/A11). Titration of synthetic peptide in cytotoxic assay demonstrated that clones activated under these conditions are as efficient as clones activated by conventional LCL stimulations. Induction of memory CTL responses required low surface density of MHC : peptide complexes, since reactivation was achieved by stimulation with T2/A11 cells pulsed with concentrations of peptide that are suboptimal for induction of target cell lysis. This protocol of activation revealed the presence of IVT-specific CTL precursors in a donor that failed to mount an IVT-specific response upon stimulation with the autologous B95.8 virus-transformed LCL. The results suggest that stimulation with synthetic peptide epitopes can be efficiently used for induction of memory CTL responses, and may be particularly helpful for the selective expansion of subdominant CTL specificities.
Clinical features of anti-chromo antibodies associated with anti-centromere antibodies
Authors: Iwai T , Muro Y , Sugimoto K , Matsumoto Y , Ohashi M 
Published: November 2003

Abstract
Anti-chromo antibodies (AChA) are autoantibodies accompanying anti-centromere antibodies (ACA). We determined the frequency and clinical significance of AChA in autoimmune rheumatic diseases. Serum samples from 252 patients with rheumatic diseases were examined by immunoblotting with HeLa nuclear extract and with recombinant N-terminus of 25-kD chromo protein (p25). AChA were detected in 28 (36%) of 77 sera with ACA. AChA were found only in ACA-positive sera. Twenty-two (79%) of 28 recognized a recombinant N-terminal portion of p25, including the chromo domain which is conserved among species. AChA were related to leucopenia, thrombocytopenia, elevated erythrocyte sedimentation rate, and existence of Sjögren's syndrome (SS). In ACA-positive patients, AChA might be a serologic indicator of systemic sclerosis (SSc), having features of systemic lupus erythematosus and/or SS or diseases other than SSc.
Cytokine mRNA expression in the liver of patients with primary biliary cirrhosis (PBC) and chronic hepatitis B (CHB)
Authors: Shindo M , Mullin G E , Braun-Elwert L , Bergasa N V , Jones E A , James S P 
Published: November 2003

Abstract
The expression of cytokine mRNA species was determined in liver biopsies from six normal subjects, 18 patients with PBC and 14 patients with hepatitis B e antigen (HBeAg)-positive CHB using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique. cDNA, obtained by reverse transcription using oligo d(T) primers, was amplified by PCR using primers specific for the coding region of seven different cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α)). The abundance of some cytokines (IL-2, IL-4, IL-5 and IFN-γ) was also estimated by semiquantitative RT-PCR, using as standards dilutions of synthetic cytokine mRNA transcripts, that could be distinguished electrophoretically from respective native cytokine mRNAs. Hepatic inflammation was assessed by a semiquantitative histologic score and by amplification of mRNA for T cell receptor (TCR)-α. mRNAs for IL-1 and IL-6 were detected in only one control liver. In CHB, mRNAs for IL-1, IL-2, IL-4, IL-5 and IFN-γ were detected in 43%, 60%, 80%, 20%, and 54% of biopsies, respectively. mRNA for IFN-γ and IL-4, but not IL-1, tended to be associated with severe inflammation. In five biopsies semiquantitative analyses revealed increased levels of mRNA for TCR-α and, when transcripts were detectable, high levels of mRNA for IFN-γ and IL-4. In PBC, mRNA for IFN-γ was detected in 60% of biopsies, but no mRNAs for IL-1, IL-2, IL-4, IL-5, or IL-6, or for TNF-α, were detected. Semiquantitative analyses revealed that absolute levels of mRNA for IFN-γ tended to correlate with the severity of hepatic inflammation. The results suggest that: (i) there may be fundamental differences in the roles that cytokines play in the hepatic inflammatory processes of PBC and CHB; and (ii) while hepatic IFN-γ mRNA expression is not specific for PBC, IFN-γ may play a prominent role in the immunopathogenesis of PBC.
Tracking of the V4–34 (VH4–21) gene in human tonsil reveals clonal isotype switch events and a highly variable degree of somatic hypermutation
Authors: Chapman C J , Mockridge C I , Hamblin T J , Stevenson F K 
Published: November 2003

Abstract
The V4–34 (VH4–21) gene has been found to encode certain IgM autoantibodies, and is mandatory for pathological IgM anti-erythrocyte antibodies of I/i specificity. The gene is also commonly used by normal IgM-positive B lymphocytes, but its involvement in B cells which have undergone class switching to IgG or IgA is less clear. In order to track V4–34 gene usage and class switching events during a normal immune response, we have probed RNA in a limited area of human tonsil. Results indicate that the V4–34 gene undergoes class switching to IgG or IgA, with the progeny either remaining unmutated or containing large numbers of somatic mutations. Mutational patterns indicate possible ‘hot spots’, and some mutations appear deleterious. At the level of individual B cells, we have tracked a clonal isotype switch event from IgM to IgA, with each retaining close to germ-line configuration. In addition, we have followed a clonal switch from a mutated IgM to IgG, with no further accumulation of somatic mutations. These data indicate that the V4–34 gene is involved in a maturing immune response, and that the routes to production of IgG or IgA antibodies are various.
Metabolic disturbance and sensitivity to endotoxin in patients with advanced cancer: relationship to lymphocyte reactivity, tumour necrosis factor (TNF) production and survival
Authors: Gough D B , Fearon K C H , Carter D C 
Published: November 2003

Abstract
Increased TNF production and impaired lymphocyte function have been individually linked with metabolic disturbance, endotoxaemia and mortality in humans. The inter-relationship between these observations was investigated in humans with cancer. In 13 patients with metastatic colorectal cancer and seven healthy volunteers, observations (n=23) included peripheral blood mononuclear cell (PBMC) TNF production, IL-2 production and phytohaemagglutinin (PHA) response; the acute-phase protein response (APPR) (serum C-reactive protein (CRP), albumin, CRP/albumin ratio), and survival. APPR correlated with survival (CRP, r=−0.689, P=0.006; CRP/albumin, r=−0.758, P=0.002; albumin, r=0.655, P=0.011), but not with TNF production. TNF production in response to in vitro endotoxin correlated with impaired lymphocyte function in patients (r=0.567, P=0.043) and in the whole group (r=0.65, P=0.001). The ratio (basal PBMC TNF production)/(lymphocyte function) correlated with CRP (r=0.569, P=0.042), CRP/albumin (r=0.617, P=0.025), endotoxin sensitivity (r=0.567, P=0.043) and survival (r=−0.545, P=0.038) in patients, and the whole group (P&lt;0.002). Impaired lymphocyte function may influence TNF production, endotoxin sensitivity and metabolic disturbance in humans with cancer. (r=Spearman correlation coefficient.)
Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals
Authors: Steger M M , Maczek C , Grubeck-Loebenstein B 
Published: November 2003

Abstract
Dendritic cells are antigen-presenting cells (APC), which are crucial for the initiation of an immune response. In spite of the well known decline of immune function in old age, no information is yet available on whether dendritic cells are also affected by the ageing process. It was therefore the aim of this study to compare peripheral blood dendritic cells (DC) from old and young healthy individuals. Using granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, DC were propagated from peripheral blood mononuclear cells (PBMC). The obtained cell populations had a typical dendritic morphology and expressed HLA class I and class II, CD23, CD32, CD40, CD44 and CD54, but not CD3 and CD19. Larger numbers of DC were obtained from old individuals than from young ones in spite of a similar expression pattern of surface molecules. DC from aged persons also survived better under in vitro culture conditions. When tested for their antigen-presenting capacity, DC from young and old individuals were equally effective in inducing the proliferation of tetanus toxoid-specific T cell clones after antigenic stimulation. Peripheral blood DC from aged individuals may thus still function as powerful APC. They may represent useful tools for immunotherapy in the aged.
Anti-inflammatory properties of human serum IgA: induction of IL-1 receptor antagonist and FcαR (CD89)-mediated down-regulation of tumour necrosis factor-alpha (TNF-α) and IL-6 in human monocytes
Authors: Wolf H M , Hauber I , Gulle H , Samstag A , Fischer M B , Ahmad R U , Eibl M M 
Published: November 2003

Abstract
A deregulated expression and/or release of large amounts of inflammatory cytokines such as IL-1 and TNF-α accounts for most pathophysiological events in a variety of systemic inflammatory diseases, the effect being mediated by the interaction of these cytokines with their respective receptors. IL-1 receptor antagonist (IL-1Ra), mainly produced by monocytes/macrophages, is an inhibitor of IL-1 activity. The present study shows that human serum IgA induces significant IL-1Ra release in human peripheral blood mononuclear cells and adherent monocytes. IgA induced higher levels of IL-1Ra than Haemophilus influenzae type b (Hib) expressing lipopolysaccharide (LPS), purified LPS or phorbol myristate acetate (PMA), without induction of IL-1β release, and even inhibited LPS-induced IL-1β release. Induction of IL-1Ra by IgA could be detected both at the mRNA and protein levels in resting and activated monocytes. Ligation of FcαR with MoAb MY-43 or treatment with human serum IgA induced protein tyrosine phosphorylation in human monocytes, and herbimycin A, a specific inhibitor of protein tyrosine kinase activity, inhibited IgA-induced IL-1Ra production, suggesting that FcαR-mediated induction of tyrosine phosphorylation is required for the IgA-induced stimulation of IL-1Ra release. In addition, triggering of FcαR with MoAb specifically down-regulated TNF-α and IL-6 release in human monocytes activated with Hib. By the induction of IL-1Ra and down-regulation of the release of inflammatory cytokines such as IL-1β, TNF-α and IL-6, interaction of IgA with human monocytes may actively contribute to the regulation of the inflammatory response.
Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression
Authors: Roos M TH L , Miedema F , Meinesz A A P , De Leeuw N A S M , Pakker N G , Lange J M A , Coutinho R A , Schellekens P TH A 
Published: November 2003

Abstract
In 219 HIV-1-infected men of the Amsterdam cohort we measured CD4+ T cell numbers and in vitro T cell responses to CD3 MoAbs with or without CD28 costimulation and phytohaemagglutinin (PHA). The value of these markers was estimated for disease progression within 4 years. CD28 expression on T cells has been related to T cell responses. CD28 costimulation considerably enhanced T cell reactivity (≈8–10-fold) with lower coefficients of variation compared with reactivity to CD3 MoAb alone (median 5 versus 20). T cell reactivity to CD3 plus CD28 MoAb was decreased during HIV-1 infection and was besides CD4+ T cell numbers the only independent predictor for progression to AIDS. Compared with the group with high CD4+ T cell numbers the relative risk (RR) for the group with intermediate levels was 2.28, with low levels 5.20. In the groups with intermediate and low CD3 plus CD28 responses the RR was 2.04 and 4.16, respectively. The combined RR for both was 4.65 and 21.63. The independence of this marker was confirmed when the group with low CD4+ T cell numbers was subdivided into groups with high, intermediate and low T cell responses. The expansion of CD8+CD28− T cells was already apparent in HIV− homosexual men, but CD8+CD28+ T cells specifically decreased in patients with AIDS. CD28 expression on T cells correlated moderately with T cell responses to CD3 plus CD28 MoAb. T cell reactivity to CD3 MoAb in the presence of CD28 MoAb is a stronger prognostic marker than T cell reactivity to CD3 MoAb alone.