bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dominant role for non-MHC gene effects in susceptibility to cyclosporin A (CsA)-induced autoimmunity
Authors: Damoiseaux J G M C , Beijleveld L J J , Van Breda Vriesman P J C 
Published: March 2003

SUMMARYLethally irradiated LEW rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period develop a graft-versus-host-like disease upon withdrawal of CsA. This T cell-mediated autoimmune disease is referred to as CsA-induced autoimmunity (CsA-AI). CsA-AI-susceptible LEW rats and resistant BN rats differ greatly in the composition of their peripheral T cell compartment. To dissect the role of MHC and non-MHC genes in the development of peripheral T cell subsets in combination with susceptibility to CsA-AI the respective MHC congenic strains (LEW-1N and BN-1L) were examined for their T cell subsets and for their ability to develop CsA-AI. In this study we show that the Th1/Th2-like cell ratio as well as susceptibility to CsA-AI are under control of the non-MHC genes. This suggests that the Th1/Th2-like cell ratio is a critical determinant for development of CsA-AI. Alternatively, resistance can be attributed to lack of target organ susceptibility due to the absence of the target autoantigen in resistant rat strains. This interpretation is rejected, since both BN as well as BN-1L rats consistently develop the characteristic macroscopic and microscopic signs of CsA-AI upon adoptive transfer with autoreactive LEW-1N and LEW T cells, respectively. Therefore, it can be concluded that the non-MHC genes encode for immune deviation and thereby determine susceptibility or resistance to CsA-AI.
Chemokine profiles in the cerebrospinal fluid (CSF) during the course of pyogenic and tuberculous meningitis
Authors: Mastroianni C M , Lancella L , Mengoni F , Lichtner M , Santopadre P , D'agostino C , Ticca F , Vullo V 
Published: March 2003

SUMMARYThe concentrations of the chemokines IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) were measured in 120 CSF samples from 23 patients with pyogenic meningitis and from 11 patients with tuberculous meningitis (TBM) and in 10 CSF from subjects with non-infectious neurological diseases. The chemokine concentrations in patients with meningitis were significantly higher than in control subjects (P &lt; 0.0001). The highest CSF levels were found for IL-8 (median 2917 pg/ml) and MCP-1 (median 2557 pg/ml), whereas those of MIP-1α were less significantly elevated (median 24 pg/ml) (P &lt; 0.0001). Patients with pyogenic meningitis had higher levels of IL-8 and MCP-1 than those with TBM (P &lt; 0.0001). In serial samples from patients with pyogenic meningitis IL-8 levels declined before MCP-1 and MIP-α. In the case of TBM, IL-8, MCP-1 and MIP-1α decreased more gradually during treatment and were detectable in the CSF for several weeks, without any characteristic time course of elimination. These data indicate that patients with pyogenic meningitis and TBM show different chemokine profiles in CSF. The distinct chemokine pattern could be responsible for a differential attraction and activation of leucocytes in the CSF which is reflected in differences in the inflammatory response and clinical course of pyogenic meningitis and TBM.
Apoptosis of Th1-like cells in experimental tuberculosis (TB)
Authors: DAS G , VOHRA H , SAHA B , AGREWALA J N , MISHRA G C 
Published: March 2003

SUMMARYTh1 cell-induced anti-mycobacterial immunity is lost during a progressive Mycobacterium tuberculosis infection in a susceptible host. This study was designed to test the mechanism of the loss of anti-mycobacterial cell-mediated immune response. We demonstrate that M. tuberculosis infection results in increased Fas expression and decreased Bcl-2 expression in CD4+ T cells. When CD4+ T cells are stimulated in vitro, they show increased apoptosis and decreased production of IL-2 and interferon-gamma (IFN-γ) but not of IL-4. These changes may result in selective apoptosis of Th1-like cells, leading to the loss of cell-mediated immune response against M. tuberculosis.
Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment
Authors: VERBON A , JUFFERMANS N , VAN DEVENTER S J H , SPEELMAN P , VAN DEUTEKOM H , VAN DER POLL T 
Published: March 2003

SUMMARYDuring TB cytokines play a role in host defence. To determine the cytokine pattern during various disease stages of TB, serum levels of IL-12, interferon-gamma (IFN-γ), IL-4, IL-6 and IL-10 were measured in 81 patients with active TB, 15 patients during therapy and 26 patients after anti-tuberculous therapy as well as in 16 persons who had been in close contact with smear-positive TB and in 17 healthy controls. IFN-γ was elevated during active TB when compared with healthy controls, declining during and after treatment. IL-12 (p40 and p70) serum levels were not significantly higher in patients with active TB compared with any of the other groups. IL-4 levels were low in all groups. IL-6 and IL-10 serum levels were elevated in patients with active TB and during treatment. In patients with active TB serum levels of IFN-γ and IL-6 were higher in patients with fever, anorexia and malaise. IL-12 levels were higher in patients with a positive smear. Cytokine levels did not correlate with localization of TB (pulmonary versus extrapulmonary), or skin test positivity. Cytokines directing a Th1 response (IL-12) or a Th2 response (IL-4) were not elevated in sera of this large group of patients with pulmonary and extrapulmonary TB. In patients with active TB, cytokines that were elevated in serum were IFN-γ, IL-6 and IL-10.
Regulation of CR3 (CD11b/CD18)-dependent natural killer (NK) cell cytotoxicity by tumour target cell MHC class I molecules
Authors: VĚTVIČKA V , HANIKÝŘOVÁ M , VĚTVIČKOVÁ J , ROSS G D 
Published: March 2003

SUMMARYPhagocyte and NK cell CR3 functions as both an adhesion molecule and an iC3b receptor mediating cytotoxic responses to microorganisms. Cytotoxic activation of iC3b receptor function requires ligation of both a CD11b I-domain site for iC3b and a lectin site located in the C-terminus of CD11b. Because tumours lack the CR3-binding polysaccharides of bacteria and fungi, iC3b-opsonized tumours do not stimulate CR3-dependent cytotoxicity. Previous studies showed that NK cells could be induced to kill iC3b-opsonized tumours with small soluble β-glucans that bound with high affinity to CR3, bypassing the absence of similar polysaccharides on tumour membranes. Because CR3 signalling requires several tyrosine phosphorylation events, it appeared possible that CR3-dependent killing of autologous tumour cells might be suppressed by NK cell inhibitory receptors for MHC class I (KIR and CD94/NKG2) whose action involves recruitment of SHP-1 and SHP-2 tyrosine phosphatases. In the current study, Epstein–Barr virus (EBV)-transformed B cells were used as targets following opsonization with iC3b. Soluble β-glucan primed CR3 for killing of iC3b-coated B cells, but autologous class I-bearing targets were 84% more resistant than class I-deficient Daudi cells. Blockade of target cell class I with a MoAb specific for a domain recognized by both KIR and CD94/NKG2 resulted in comparable killing of class I+ B cells. By contrast, another MoAb to class II had no effect on cytotoxicity. These data suggest that NK cell recognition of class I suppresses CR3/tyrosine kinase-dependent cytotoxicity in the same way as it suppresses cytotoxicity mediated by other tyrosine kinase-linked receptors such as FcγRIIIA (CD16).
Expression of killer inhibitory receptors on cytotoxic cells from HIV-1-infected individuals
Authors: GALIANI M D , AGUADO E , TARAZONA R , ROMERO P , MOLINA I , SANTAMARIA M , SOLANA R , PEÑA J 
Published: March 2003

SUMMARYDysfunction of cytotoxic activity of T and natural killer (NK) lymphocytes is a main immunological feature in patients with AIDS, but its basis are not well understood. It has been recently described that T and NK cell-mediated cytotoxicity can be regulated by HLA killer inhibitory receptors (KIR). In this work, we have determined on cytotoxic T cells and NK cells from HIV-1-infected individuals the expression of the following KIR molecules: p58, p70, and ILT2 (immunoglobulin-like family KIR) as well as CD94 and NKG2A (C-lectin-type family KIR). With some exceptions, no significant changes were found on the expression of immunoglobulin-like KIR in either CD8+ or CD56+ cells. Interestingly, the percentages of CD8+ and CD56+ cells expressing CD94 were significantly increased in these individuals. We also show that, in vitro, IL-10 up-regulates CD94 expression on CD8+ and CD56+ cells obtained from normal individuals, suggesting that the augmented expression observed in HIV-infected individuals could be related to the high levels of IL-10 previously described in HIV-1-infected individuals.
Evidence for control of tumour necrosis factor-alpha (TNF-α) activity by TNF receptors in patients with proliferative diabetic retinopathy
Authors: LIMB G A , SOOMRO H , JANIKOUN S , HOLLIFIELD R D , SHILLING J 
Published: March 2003

SUMMARYTNF-α has been implicated in the pathogenesis of insulin- dependent diabetes mellitus (IDDM). At present there are no studies linking serum levels of soluble TNF receptors (sTNF-R) to the development of diabetic microvascular complications such as proliferative diabetic retinopathy (PDR), or to the production of TNF-α in these patients. We investigated serum levels of sTNF receptors (sTNF-RI and sTNF-RII) in IDDM patients with or without PDR, and related these to the in vitro production of TNF-α upon activation of whole blood and isolated mononuclear cells (MNC). We observed higher serum levels of sTNF-RI in IDDM patients with active (range 945–6630 pg/ml; P = 0.029) or quiescent PDR (range 1675–4970 pg/ml; P = 0.00092) than in individuals with IDDM without retinopathy (range 657–2617 pg/ml) or healthy controls (range 710–1819 pg/ml; P = 0.0092 and 0.0023, respectively). Increased serum levels of sTNF-RII were also seen in IDDM patients with active PDR (range 1749–5218 pg/ml; P = 0.034) or quiescent PDR (range 1494–5249 pg/ml; P = 0.0084) when compared with disease controls (range 1259–4210 pg/ml) or healthy subjects (range 1237–4283 pg/ml). Whole blood production of biologically active TNF-α was lower in PDR patients than in disease (P = 0.04) and healthy controls (P &lt; 0.005), contrasting with a higher production of TNF-α by lipopolysaccharide (LPS)-activated MNC from PDR patients (P = 0.013). Inhibition of TNF-α by TNF-R in plasma supernatants of activated blood from PDR patients was demonstrated by increase of TNF-α activity in the presence of anti-TNF-RI and anti-TNF-RII antibodies. These observations suggest that abnormalities in TNF-α production and control may operate during the development of microvascular complications of diabetes mellitus.
Increased interferon-gamma (IFN-γ) levels producedin vitroby alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon
Authors: MOLTENI M , DELLA BELLA S , MASCAGNI B , BAZZI S , ZULIAN C , COMPASSO S , LESSI M , SCORZA R 
Published: March 2003

SUMMARYThe aim of the present study was to analyse the in vitro proliferation and cytokine production by alloantigen-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients affected by systemic sclerosis (SSc) and patients with Raynaud's phenomenon (RP). In SSc patients the proliferation of PBMC stimulated in vitro with alloantigens was significantly increased compared with healthy subjects, while no differences were observed for RP patients. Lymphocytes from SSc patients also produced larger amounts of IFN-γ compared with healthy controls. However, patients with clinically active disease had lower IFN-γ levels than those found in clinically stable patients. Patients affected by RP showed significantly higher levels of IFN-γ than healthy subjects. Analysis at the clonal level of the lymphocyte subsets involved in alloantigen stimulation in one patient affected by active SSc, and one subject with RP confirmed the results obtained using PBMC. In particular, in the RP patient but not in the SSc patient, we observed a population of CD4+ T cells which proliferated to alloantigens in vitro and produced high levels of IFN-γ. We suggest that T lymphocytes producing high levels of IFN-γ might play a protective role in RP patients and in established scleroderma.
Detection of antibodies directed against the cytoplasmic region of the human acetylcholine receptor in sera from myasthenia gravis patients
Authors: TZARTOS S J , REMOUNDOS M 
Published: March 2003

SUMMARYThe nicotinic acetylcholine receptor (AChR) is the autoantigen in the human autoimmune disease myasthenia gravis (MG). Anti-AChR antibodies in MG sera bind mainly to conformational epitopes, therefore the determination of their specificities requires the use of native AChR. Antibody competition studies suggest that most MG antibodies are directed against the extracellular part of the molecule, whereas antibodies directed against the cytoplasmic region of the AChR have not been detected. To determine whether even small quantities of such antibodies exist in MG sera, we performed competition experiments based on the inhibition by MG sera of the binding of MoAbs to the human AChR, rather than inhibition by MoAbs of the binding of MG sera performed earlier. When MoAbs directed against cytoplasmic epitopes on the α or β subunits (α373–380 and β354–360) were used as test MoAbs, 17% or 9% of MG sera inhibited the binding of the anti-α or anti-β subunit MoAbs, respectively, by ≥ 50%. Non-specific inhibition was excluded. These results suggest the presence, in several MG sera, of antibodies directed against cytoplasmic regions of the AChR; yet these antibodies seemed to represent a relatively small proportion of the total anti-AChR antibodies. The corresponding epitopes may be involved in the inducing mechanisms in certain MG cases, and knowledge of the presence of such antibodies may be useful in understanding the autoimmune mechanism involved in MG.
The effects of extracorporeal whole body hyperthermia on the functional and phenotypic features of canine peripheral blood mononuclear cells (PBMC)
Authors: KEARNS R J , RINGLER S , KRAKOWKA S , TALLMAN R , SITES J , OGLESBEE M J 
Published: March 2003

SUMMARY
In this study the effect of transient 42.3°C whole body hyperthermia (WBH) on the distribution of PBMC phenotypes and in vitro blastogenic responsiveness was determined in dogs. Hyperthermia (n = 6) was induced by heating venous blood during extracorporeal circulation (venous perfusion WBH); perfused non-heated dogs (n = 4) were used as controls. Both euthermic and hyperthermic perfusion produced transient lymphopenia which normalized in controls after perfusion but persisted in hyperthermic animals throughout the 8-day post-perfusion observation interval. The transient lymphopenia in control dogs was non-selective. In contrast, WBH-associated lymphopenia was selective, in that CD5+ T lymphocytes were more sensitive to hyperthermia than sIg+ B cells and, within the T cell compartment, suppressor (CD8+) cells were more sensitive to hyperthermic stress than helper (CD4+) lymphocytes. Functional analyses showed that WBH caused persistent suppression of PBMC blastogenesis in response to T cell phytomitogens. Increased plasma cortisol levels were correlated to peak lymphopenia and hyporesponsiveness to phytomitogens. Despite these alterations, high grade WBH was well tolerated and there was no evidence of opportunistic infection.
Gene expression of 5-lipoxygenase and LTA4 hydrolase in renal tissue of nephrotic syndrome patients
Authors: MENEGATTI E , ROCCATELLO D , FADDEN K , PICCOLI G , DE ROSA G , SENA M , RIFAI A 
Published: March 2003

SUMMARY
Leukotrienes (LT) of the 5-lipoxygenase pathway constitute a class of potent biological lipid mediators of inflammation implicated in the pathogenesis of different models of experimental glomerulonephritis. The key enzyme, 5-lipoxygenase (5-LO), catalyses oxygenation of arachidonic acid to generate the primary leukotriene LTA4. This LT, in turn, serves as a substrate for either LTA4 hydrolase, to form the potent chemoattractant LTB4, or LTC4 synthase, to produce the powerful vasoconstrictor LTC4. To investigate the potential role of LT in the pathogenesis of human glomerulonephritis with nephrotic syndrome, we examined the gene expression of 5-LO and LTA4 hydrolase in renal tissue of 21 adult patients with nephrotic syndrome and 11 controls. The patients consisted of 11 cases of membranous nephropathy (MN), seven focal and segmental glomerulosclerosis (FSGS), two non-IgA mesangial glomerulonephritis and one minimal change disease. Total RNA purified from renal tissue was reverse transcribed into cDNA and amplified with specific primers in a polymerase chain reaction (RT-PCR). Eight patients' renal tissue, four MN and four FSGS, co-expressed 5-LO and LTA4 hydrolase. In situ hybridization analysis revealed 5-LO expression and distribution limited to the interstitial cells surrounding the peritubular capillaries. Comparative clinical and immunohistological data showed that these eight patients had impaired renal function and interstitial changes that significantly correlated with 5-LO expression. These findings suggest that leukotrienes may play an important role in the pathogenesis of MN and FSGS. These results are also relevant to elucidating the pathophysiologic mechanisms which underlie progression to renal failure in these diseases.
Cytokine-producing cells in peripheral blood of children with coeliac disease secrete cytokines with a type 1 profile
Authors: HANSSON T , DANNÆUS A , KLARESKOG L 
Published: March 2003

SUMMARY
Coeliac disease (CoD) is a small intestinal disorder characterized by crypt cell hyperplasia and villous atrophy, and the production of cytokines from T cells and macrophages are of importance for the histological changes seen in CoD. A peroral immunization with an antigen, which gives rise to a mucosal immune response, may increase the levels of circulating cytokine-producing cells, and we wanted to obtain a better picture of an eventual emergence of activated circulating T cells in the peripheral blood in children with CoD. The cytokine expression of interferon-gamma (IFN-γ), IL-4, IL-6 and IL-10 was measured at the single-cell level by an ELISPOT method in 38 children with CoD. The numbers of IFN-γ-producing cells in the peripheral blood was increased in children with untreated CoD (P &lt; 0.01) and after gluten challenge (P &lt; 0.05) compared with healthy controls. Also, the numbers of IL-6-producing cells were increased (P &lt; 0.05) after gluten challenge compared with the healthy controls. A paired comparison showed that the numbers of IFN-γ-producing cells increased after gluten challenge (P &lt; 0.05), whereas no such change was seen for IL-4- or IL-10-producing cells. There were no differences in the numbers of IFN-γ-producing cells between the group of children with treated CoD and the groups of untreated or challenged CoD children. IL-4 production correlated with serum levels of total IgE. These results show that circulating mononuclear cells in children with active CoD secrete cytokines compatible with a type 1 response.
Absence of significant Th2 response in diabetes-prone non-obese diabetic (NOD) mice
Authors: HARTEMANN A H , RICHARD M-F , BOITARD C 
Published: March 2003

SUMMARYAccumulating evidence suggests that Th1 T cells play a pivotal role in the development of autoimmune diabetes. Conversely, promoting a Th2 response inhibits disease progression. However, it has not been determined whether Th2 cells are regulatory T cells that fail at the time of diabetes development in naive non-diabetic NOD mice. Therefore, in order to evaluate cytokine secretion by spleen and islet infiltrating T cells in NOD mice at different stages of the autoimmune process, we developed an ELISPOT assay that detects IL-2, IL-4, and interferon-gamma (IFN-γ) secretion in vitro at the single-cell level. We showed that, whatever the age considered, IFN-γ is predominantly secreted, and that no IL-4-secreting cells are detected in the islets of male and female NOD mice. Spleen cells from 8-week-old female NOD mice, which include regulatory suppressor T cells, do not secrete IL-4, either upon presentation of islet cell antigens in vitro, or after transfer in vivo, but do secrete IFN-γ. IFN-γ secretion by T cells from diabetic mice results from CD4 but not CD8 T cells in transfer experiments into NOD/severe combined immunodeficient (SCID) recipients. These results suggest that (i) detection of regulatory CD4 T cells in NOD mice is not paralleled by a Th2 response; (ii) β cell destruction does not depend on a switch from a Th2 to a Th1-type response; and (iii) CD8 T cells do not participate in induction of diabetes by secreting IFN-γ.
Mode of delivery directs the phagocyte functions of infants for the first 6 months of life
Authors: GRÖNLUND M M , NUUTILA J , PELTO L , LILIUS E M , ISOLAURI E , SALMINEN S , KERO P , LEHTONEN O P 
Published: March 2003

Abstract
Factors that direct the immune responsiveness of the newborn beyond the immediate post-natal period are not known. We investigated the influence of mode of delivery and type of feeding on the phagocyte activity during the first 6 months of life. Sixty-four healthy infants (34 delivered vaginally and 30 by elective Caesarean section) were studied at birth and at the ages of 2 and 6 months. Phagocyte functions were studied by measuring the chemiluminescence (CL) activity of whole blood and isolated leucocytes and by investigating the expression of phagocyte receptors (FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16), CR1 (CD35), CR3 (CD11b) and FcαR (CD89)) on neutrophils, monocytes and eosinophils by using receptor-specific MoAbs and immunofluorescence flow cytometry. Infants born by elective Caesarean section had significantly higher CL activity than those delivered vaginally during the entire 6-month follow up. In addition, infants who received formula feeds had significantly higher CL activity at 6 months of age and higher expression of FcγRI-, Fcα- and CR3-receptors on neutrophils than infants exclusively breast-fed. We suggest that stress reaction associated with labour influences the phagocytic activity measured in the cord blood but later during infancy the intraluminal antigens, gut microflora and diet, become important determinants in immune programming of human individuals.
Analysis of Epstein–Barr virus (EBV) receptor CD21 on peripheral B lymphocytes of long-term EBV− adults
Authors: JABS W J , PAULSEN M , WAGNER H J , KIRCHNER H , KLÜTER H 
Published: March 2003

AbstractPrimary infections with EBV are rarely observed after the age of 20. Some individuals even remain seronegative all their lives. Previously, a lack of EBV receptors on B cells of persistently EBV− adults was described as a reason for long-term EBV-seronegativity. The present study examined the CD21 receptor status of 20 repeatedly EBV− healthy adults and 32 EBV+ volunteers by means of flow cytometry. CD21 molecules on the surface of CD19+ B cells were quantified using anti-IgG-coated microbeads. The percentage of CD19+/CD21+ B lymphocytes was slightly lower in the peripheral blood of EBV−donors, but the CD21 antibody binding capacity on CD19+ B cells showed no significant differences between EBV− and EBV+ adults. In vitro studies showed an equally good EBV transformability of peripheral B lymphocytes of EBV− and EBV+ donors. Since HLA-DR was recently described as a co-receptor for EBV infection of B cells, we also determined HLA-DRB1 alleles in the EBV−group. We found a significant negative association of EBV-seronegativity with HLA-DR13 in comparison with 111 healthy blood donors. In summary, a biologically significant lack of the EBV receptor CD21 on peripheral B lymphocytes of persistently EBV− adults was excluded as a reason for long-term EBV-seronegativity.