bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphocytes infiltrating normal human lung and lung carcinomas rarely express γδ T cell antigen receptors
Authors: FAJAC I , TAZI A , HANCE A J , BOUCHONNET F , RIQUET M , BATTESTI J P , SOLER P 
Published: July 2010

SUMMARYIt has been suggested that T lymphocytes expressing γδ T cell receptors (TCR) could play an important role in the defence of epithelia against infection and neoplastic transformation, but the potential for γδ T lymphocytes to serve these functions in human respiratory epithelium has received little attention. In this study, we used immunohistochemical techniques and specific monoclonal antibodies to characterize the number and distribution of T lymphocytes expressing αβ und γδ TCR in normal human lung and in lung carcinomas. T lymphocytes present in normal bronchi and alveolar parenchyma were predominantly of the αβ TCR phenotype. whereas γδ T lymphocytes represented only 1·1 ±0·7% and 1·3±0·5% of total CD3+ lymphocytes respectively. An important lymphocytic infiltration was noted in the stroma of all primary lung carcinomas examined, and some T lymphocytes were also present infiltrating between tumour cells. These T lymphocytes were almost entirely αβ T cells and only rare γδ T ceils were found, regardless of the histologic type of carcinoma (0·8±0·1% of CD3+ T cells). This study demonstrates that T cells present in normal bronchi and lung parenchyma and those infiltrating primary lung carcinomas express predominantly αβ TCR. These findings do not support the conclusion that γδ T lymphocytes play an important role cither in the defence of human lung epithelia or in immune responses directed against primary lung carcinomas.
Clusterin in renal tissue: preferential localization with the terminal complement complex and immunoglobulin deposits in glomeruli
Authors: FRENCH L E , TSCHOPP J , SCHIFFERLI J A 
Published: July 2010

SUMMARYThe membrane attack complex (MAC) of complement is activated by immune and non-immune mechanisms in the kidney. MAC has been found associated with glomerular immune deposits, but also to cell remnants, particularly along tubules and in vessel walls. Clusterin and S-protein (vitronectin) bind to MAC, rendering it cytolytically inactive. Both have been found associated with MAC in renal tissue. Here we analysed the deposition of clusterin and S-protein in 118 renal biopsies relative to the localization of the MAC using MoAbs. Statistical analysis was performed comparing no or little versus evident or strong staining by immuofluorescence (IF). In glomeruli, out of the 92 biopsies where both MAC and immunoglobulins were evaluated, deposits of MAC were found in the presence (32 out of 41) but also in the absence of immunoglobulins (20/51). Clusterin and S-protein deposits were seen, respectively, in 25 out of 61 and 36 out of 61 biopsies containing glomerular MAC and almost never in its absence (one out of 50 for both). The association of the two inhibitors with MAC was observed mainly in glomeruli containing immunoglobulin deposits (respectively, 21 out of 32 and 25 out of 32), but not when immunoglobulins were absent (three out of 20 and seven out of 20) (coefficient of concordance, K= 0·47 and 0·43). The localization of MAC along tubules and in vessels was easily identified in most biopsies (93 out of 118) and was accompaied by S-protein in most cases (tubules, 86 out of 93; vessels, 82 out of 93) (K= 0·58 and 0·57 respectively) but not by clusterin (28 out of 93 and 24 out of 93). These results suggest that clusterin does not co-localize with MAC whenever there is formation and fixation of the MAC. It seems that clusterin has a particular affinity for MAC which is associated with immunoglobulin. This observation should help to distinguish between the different forms of MAC, and might indicate that MAC associated with immunoglobulin is essentially in its cytolytically inactive form.
Increased and prolonged production of specific polymeric IgA after systemic immunization with tetanus toxoid in IgA nephropathy
Authors: LAYWARD L , ALLEN A C , HARPER S J , HATTERSLEY J M , FEEHAHLY J 
Published: July 2010

SUMMARYIgA nephropathy (IgAN) is a chronic form of glomerulonephritis which is characterized by THE deposition in the glomerular mesangium of polymeric IgA (pIgA), the source of which is unknown. In order to investigate the production of pIgA in IgAN, patients were immunized systemically with tetanus toxoid (TT). Two weeks after immunization patients and controls responded to TT with an IgA response of similar magnitude. HPLC separation of sera showed that patients with IgAN produce significantly more plgA anti-TT than controls (7·7 versus 2·88 arbitrary units; P 0·04). At this time, 33% of serum IgA anti-TT produced by patients with IgAN was polymeric, compared with 21% produced by controls (P &lt; 0·02). Monomeric IgA (mIgA) anti-TT levels were similar in both groups. Four weeks after immunization the proportion of pIgA anti-TT in controls and patients was significantly reduced from the 2 week level (from 21% to 0%, P &lt; 0·02 for controls: and from 33% to 8%, P 0·001, for patients). Only four out of 12 controls had any detectable pIgA anti-TT at this time compared with nine out of 10 patients with IgAN (P&lt;0·05), and IgAN patients produced proportionally more pIgA anti-TT than did controls (median 8%, interquartile ranges (IQR) 4–10%versus 0% IQR 0–3%; P &lt; 0·01). HPLC analysis under acid conditions did not alter the pattern of pIgA and mIgA anti-TT, suggesting that the high molecular weight IgA fraction was not due to complexes. These data indicate that circulating pIgA results (at least in part) from a systemic response to antigen, which may be exaggerated in IgAN.
A somatically mutated VκIV gene encoding a human rheumatoid factor light chain
Authors: GAUSE A , KÜPPERS R , MIERAU R 
Published: July 2010

SUMMARYThe light chain of an IgA K rheumatoid factor (RF) produced by a hybridoma derived from a patient with rheumatoid arthritis (RA) has been shown to belong to the VκIV family. This RF light chain has 31 nucleotide differences compared with the single VκIV germline gene reported for the human genome. The patient's VκIV germline gene was sequenced, using the polymerase chain reaction (PCR), and shown to be identical to that previously reported. This demonstrates that the RF light chain is the product of a somatically mutated gene. A comparison with other known VκIV sequences shows that the RF light chain has more replacement mutations than most of the known VKIV light chains.
VLA family in rheumatoid arthritis: evidence forin vivoregulated adhesion of synovial fluid T cells to fibronectin through VLA-5 integrin
Authors: GARCÍA-VICUÑA R , HUMBRÍA A , POSTIGO A A , LÓPEZ-ELZAURDIA C , DE LANDÁZURl M O , SÁNCHEZ-MADRID F , LAFFÓN A 
Published: July 2010

SUMMARYAdhesion of T cells to extracellular matrix (ECM) proteins through VLA integrin receptors is crucial for lymphocyte trafficking, tissue localization and inflammatory function. We have investigated the expression of different VLA integrins (VLA-l-5) on peripheral blood (PB) and synovial fluid (SF) T lymphocytes from patients with rheumatoid arthritis (RA). Their expression on different cell types from synovial membrane (SM) is also reported. The role of VLA-4 fibronectin (FN) receptors in the interaction of activated SF T cells from RA patients with a 38-kD fragment of FN has been previously demonstrated. Here we have focused functional studies on VLA-5 as an alternative FN receptor for RA T cells. A significant higher proportion of SF T cells were able to bind to an 80-kD fragment of FN, containing the Arg–Gly–Asp (RGD) cell binding site, compared with PB T cells. This attachment was almost completely inhibited by anti-VLA-5 MoAbs as well as by RGD peptides. This enhanced capability by SFT cells appears to be independent of the level of the surface expression of the receptor and correlates better with their activation state as determined by the expression of the activation molecule AIM (CD69). The evidence for the expression of VLA heterodimers on both SF and SM cells from R.A patients suggests the possible implication of ECM proteins in mediating and perpetuating inflammation in vivo.
Successful transfer of collagen-induced arthritis to severe combined immunodeficient (SCID) mice
Authors: WILLIAMS R O , PLATER-ZYBERK C , WILLIAMS D G , MAINI R N 
Published: July 2010

SUMMARYWe describe the adoptive transfer of erosive arthritis to an immunodeficient host. Spleen cells from arthritic DBA/I mice (H-2q). immunized 4–6 weeks previously with bovine type II collagen in adjuvant, were transferred intraperitoncally into SCID mice (H-2d). SCID recipient mice also received native or denatured type II collagen (100 μg intraperitoncally) at the time of cell transfer. Arthritis developed in live out of five mice approximately 2 weeks after injection of cells plus native collagen, whereas animals injected with cells plus denatured collagen did not show any clinical or histological evidence of arthritis. The minimum graft size required for successful transfer of arthritis was established at 107 DBA/1 spleen cells. Histological examination of the joints of arthritic SCID recipient mice revealed synovitis, fibrosis and erosion of cartilage and underlying bone. Mean circulating levels of anti-type II collagen IgG were found to be significantly higher in mice injected with native collagen than those injected with denatured collagen (40 μg/ml and &lt; 1 μg/ml, respectively). The ability to transfer collagen-induced arthritis adoptively should facilitate the study of the cellular requirement and pathological mechanisms involved in the induction of this arthropathy.
Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice
Authors: HOLMDAHL R , JANSSON L , ANDERSSON M , JONSSON R 
Published: July 2010

SUMMARYDBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus formation without T cell infiltration and only limited MHC class II expression. Specific pathogen-free DBA 1 mice from different sources developed the same disease. Analyses of inbred mouse strains with various genetic backgrounds and F1 hybrids revealed that the disease is genetically dependent of DBA/1 recessive genes. However, F1 hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/1 mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing effects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development of arthritis is dependent on hormonal and behavioural mediated effects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristane-induced arthritis. We conclude that the spontaneously developing arthritis in the normal DBA/1 strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis.
A model for the investigation of factors influencing haemorrhagic necrosis mediated by tumour necrosis factor in tissue sites primed with mycobacterial antigen preparations
Authors: AL ATTIYAH R , ROSEN H , ROOK G A W 
Published: July 2010

SUMMARYMycobacterial lesions and skin sites challenged with soluble mycobacterial antigen are very sensitive to the necrotizing effect of tumour necrosis factor (TNF). We have used a model that permits separate quantitative assessment of swelling and haemorrhage to show that when these reactions are elicited in mice that have not been deliberately immunized, pretreatment of the mice with lipopolysaccharide (LPS), or with a MoAb to CR3 which blocks emigration of myeloid cells into the tissues, will block both the swelling and the haemorrhage. On the other hand, treatment with an inhibitor of platelet-activating factor (PAF), or with misoprostol (a synthetic prostaglandin E1 analogue), or with cobra venom factor (CVF) which depletes complement, preferentially blocks the haemorrhagic component, while leaving the swelling relatively unaltered. As swelling occurs before the haemorrhage is seen, it is possible that these factors act at a late stage in the cascade of events leading to the tissue damage. However, LPS and CVF were able to inhibit swelling and haemorrhage in the massive reactions elicited in pre-immunized animals, whereas the PAF inhibitor had no detectable effect.
Different lymphoid cell populations produce varied levels of neopterin, β2-microglobulin and soluble IL-2 receptor when stimulated with IL-2, interferon-gamma or tumour necrosis factor-alpha
Authors: HOFMANN B , BASS H , NISHANIAN P , FAISAL M , FIGLIN R A , SARNA G P , FAHEY J L 
Published: July 2010

SUMMARYImmune activation is central to many immune disorders. Clinical investigations have shown that immune activation can be quantified by measurements of soluble immune activation products in serum. Most in vitro studies of these immune activation products have focused on single products. In this study the specific cell sources and the major lymphokines inducing multiple activation products were investigated. In vitro addition of interferon-gamma (IFN-γ) or IL-2 stimulated peripheral blood mononuclear cells to produce neopterin, β2-microglobulin (β-M) and soluble IL-2 receptor (sIL-2R). These two lymphokines can act independently, because neutralizing antibodies to one of the lymphokines did not block the inducing activity of the other. Tumour necrosis factor-alpha (TNF-α) was also investigated and shown to be a less powerful inducer than IL-2 or INF-γ. Separated lymphoid subpopulations responded differently to specific lymphokines. Monocytes produced only neopterin and only in response to INF-γ. T cells released β2-M and sIL-2R in response to IL-2. B cells, however, were capable of producing all three immune activation products. Neopterin production in B cells was induced by either INF-γ of IL-2, indicating that B cells have additional mechanisms for responding to lymphokines. To investigate whether these in vitro findings also occur in vivo, sera from patients who had received either rIL-2 or INF-γ treatment were tested. INF-γ administration led to substantial increases in serum neopterin but only a moderate β2-M increase and no increase in the serum sIL-2R levels. rIL-2 administration caused a substantial increase of all three serum immune activation products, consistent with our in vitro findings. The results confirm that increased serum levels of soluble immune activation products are indicators of increased cytokine production by lymphocytes and monocytes and also that B cells can be a prominent source of immune activation products.
Serum-induced suppression of interferon (IFN) activity. Lack of evidence for the presence of specific autoantibodies to IFN-α in normal human sera
Authors: HANSEN M B , SVENSON M , BENDTZEN K 
Published: July 2010

SUMMARYIgG antibodies binding to different IFN species have been described in sera of healthy and diseased individuals. Human serum immunoglobulins have also been shown to interfere with IFN bioactivity. To characterize these antibodies, human recombinant IFN-α2A (rIEN-α) was radioiodinated, and ligand binding studies were performed in human sera as well as on the human cell line A-549 in the presence of human serum. 125I-rIFN-α bound to serum factors of healthy individuals. However, less than 3% of the binding was to IgG and the binding was non-saturable and therefore most likely non-specific. 125I-rIFN-α bound to receptors on A-549 cells, and the ligand-receptor complexes appeared to internalize. However, both cell binding and internalization of 125I-rIFN-α were independent of the presence of human serum. We conclude that normal human sera do not contain detectable autoantibodies to rIFN-α.
Involvement of the H+/K+-ATPase α subunit as a major antigenic protein in autoimmune gastritis induced by neonatal thymectomy in mice
Authors: KONTANI K , TAGUCHI O , TAKAHASHI T 
Published: July 2010

SUMMARY
Autoimmune gastritis develops spontaneously in approximately 60% of BALB/c mice thymectomized neonatally. Histologically and clinically it is similar to the atrophic gastritis associated with pernicious anaemia in humans. Here we identified antigenic protein relating to the pathogenesis of autoimmune gastritis in these mice. All sera from 32 thymectomized mice with gastritis contained autoantibodies to the vesicular fraction prepared from rat gastric parietal cells. Immunoblot analysis revealed all of these to react with a 94-kD protein corresponding in molecular mass with the H+/K+-ATPase α subunit. Some sera were also reactive with 65-85-kD and/or 60-kD proteins, whose sizes correspond to the H+/K+-ATPasc β subunit and intrinsic factor, respectively. The finding that immuno-adsorption with these sera resulted in reduction of H+/K+-ATPase activity in the vesicular fraction, supported a conclusion of H+/K+-ATPase α and/or β subunits as the antigenic proteins. After immunization of normal syngeneic mice with various doses of gastric parietal cells or their vesicular fraction, all sera from animals demonstrating atrophic gastric mucosa with lymphocyte infiltration reacted with the H+/K+-ATPase α subunit. No antibodies to other proteins were induced even in mice immunized with higher doses of antigen. We therefore conclude that H+/K+-ATPase α subunit is important as the target antigen in pathogenesis of autoimmune gastritis in neonatally thymectomized mice, probably due to a high affinity for the MHC molecule.
Functionally active complement is present in human ovarian follicular fluid and can be activated by seminal plasma
Authors: PERRICONE R , PASETTO N , DE CAROLIS C , VAQUERO E , PICCIONE E , BASCHIERI L , FONTANA L 
Published: July 2010

SUMMARYHuman ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma of the FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed.
Mycobacterial 65-kD heat shock protein induces release of proinflammatory cytokines from human monocytic cells
Authors: FRIEDLAND J S , SHATTOCK R , REMICK D G , GRIFFIN G E 
Published: July 2010

SUMMARYMonocytes having phagocytosed mycobacteria are known to present the bacterial 65-kD heat shock protein (hsp) on their cell surface to αβ and γδ T lymphocytes. Cytotoxic CD4+ cells may then lyse monocytes expressing mycobacterial 65-kD hsp. However, it is not known whether 65-kD hsp directly stimulates monocyte functions other than antigen presentation. This study has demonstrated that following extraction of bacterial lipopolysaccharide, purified recombinant mycobacterial 65-kD hsp may directly activate THP-1 cells, a human monocytic line, to accumulate mRNA for and secrete tumour necrosis factor (TNF), a cytokine important in granuloma formation, the characteristic host immune response to mycobacterial infection. TNF gene expression and secretion following stimulation by hsp was dose-dependent and abolished by heat-induced proteolysis. Subsequently, THP-1 cells secreted IL-6 and IL-8, cytokines involved in recruitment and differentiation of T lymphocytes. The data indicate that secretion of proinflammatory cytokines from monocytes activated by mycobacterial 65-kD hsp may be important in the host immune response and in the development of antigen-specific T cell-mediated immunity.
Tumour-infiltrating lymphocytes in primary melanoma: functional consequences of differential IL-2 receptor expression
Authors: BECKER J C , SCHWINN A , DUMMER R , BURG G , BRÖCKER E-B 
Published: July 2010

SUMMARYTumour-infiltrating lymphocytes (TIL) have been isolated from early primary melanoma (Clark level III) and expanded in vitro using culture conditions with low concentrations of IL-2 (50 U/ml). Immediately after isolation TIL consisted of mainly CD3+ T cells, and the portion of CD56+ natural killer (NK) cells was below 20%. Fresh TIL cultures could be distinguished by CD25 expression since some contained up to 33%, others less than 5% CD25+ cells. These showed differences in subsequent development during in vitro expansion. CD25-cxprcssing cultures remained stable in their phenotype, whereas the second TIL type showed major changes: CD3 (ca 70–30%) expression decrease. CD25 (ca 5–35%) and CD56(ca 15–55%) expression increase. The TIL type, which remained dominated by CD3+ T cells, killed autologous tumour cells efficiently (51Cr-rclcase greater than 30% at a E/T ratio of 20:1). which could be blocked by MoAbs against MHC class I molecules. In contrast, the other TIL type exhibited weak cytotoxicity (less than 17% 51Cr-release at an E/T ratio of 20:1) against the autologous tumour. Therefore, the expression of CD25 on freshly isolated TIL is a good marker for tumour specificity of in vitro expanded TIL.
Modulation of CD4 by suramin
Authors: ALLEN P D , JOHNSTON D H , MACEY M G , WILLIAMS N S , NEWLAND A C 
Published: July 2010

SUMMARYSuramin is a polysulphonated compound which can selectively bind to, and inhibit the activity of, a wide range of growth factors. There has been renewed interest recently in suramin as an anti-cancer agent and therefore we have studied its effects on lymphocyte subset populations and recombinant human IL-2 (rhIL-2) activation on lymphocytes in vitro. In the presence of rhIL-2 (1000 U/ml), suramin (200 μg/ml) caused a decrease in percentage of cells expressing the predominantly T cell antigen CD3; no change in percentage of cells expressing the T supprcssor/cytotoxic subset antigen. CD8; a small rise in those expressing the natural killer cell antigen. CD56: and a large significant fall in those expressing the T helper subset antigen CD4 (48.51%versus 27.97%; P&lt;0.00l). CD4 modulation by suramin was also found on the CD4+ cell lines CEM and MOLT-4. The effect of suramin on rhIL-2-induced activation antigen expression remains equivocal, since a small rise in CD25 expression and small falls in CD7I and HLA-Dr expression were recorded. The modulatory effect of suramin on CD4 expression was not reversible over a 96-h culture period in its continued presence. However, on removal of suramin by extensive washing, recovery of CD4 expression was detected within 24 h. Suramin-induccd modulation, but not PMA-induccd modulation, could be partially inhibited by preincubation with lyrphostin (12 μm). a tyrosine kinase inhibitor.