bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow cytometric analysis of the stimulatory response of T cell subsets from normal and HIV-1+ individuals to various mitogenic stimuliin vitro
Authors: MEDINA E , BORTHWICK N , JOHNSON M A , MILLER S , BOFILL M 
Published: July 2010

SUMMARYA novel technique is described which allows the study of the responses of T cell subpopulations stimulated in bulk cultures without interfering with cell-cell interactions. The number and phenotype of lymphoblasts developing following stimulation with phytohaemagglutinin (PHA), anti-CD3, staphylococcal protein A (SPA) and pokeweed mitogen (PWM) was determined in HIV-P and HIV-1+ patients using a new five-parameter flow cytometric method. We found that normal T ceils responded faster to PHA than lo any of the other mitogens tested. The peak of the PHA response occurred on day 3. followed by anti-CD3 and SPA on day 4 and PWM mitogen on day 5. Although PHA and anti-CD3 stimulated up to 95% and 80% of lymphocytes, respectively, SPA and PWM stimulated only 40% and 30% of cells, respectively. A defective T cell response was observed in lymphocytes cultured from asymptomatic HlV-1+ patients compared with negative controls. This loss of response was related to a selective mortality of T cells following mitogenic stimulation, referred to as activation-associated lymphocyte death (AALD). The results showed that stronger mitogens (PHA and anti-CD3) induced AALD in a larger proportion (50–60%) of T cells than weaker mitogens such as SPA and PWM (30–40%). and that AALD affected different lymphocyte subsets to different extents. AALD occurred more frequently in total CD4+ and CD45RO+ T ceils compared with CD4+ and CD45RA+ T cells, but memory CD4+ T cells were the population most severely affected in samples from HIV-I+ donors.
Primary T lymphocyte immunodeficiency associated with a selective impairment of CD2, CD3, CD43 (but not CD28)-mediated signal transduction
Authors: RODRIGUEZ-GALLEGO C , ARNAIZ-VILLENA A , CORELL A , MANZANARES J , TIMON M , PACHHCO A , REGUEIRO J R 
Published: July 2010

SUMMARYA 2-year-old female with important signs of immune response failure against virus, bacteria, fungi and protozoa and no obvious humoral or lymphocyte phenotypical defect was studied. Both peripheral blood mononuclear cells and IL-2-dependent T cell lines derived from the patient showed a severe selective T cell activation impairment via CD2, CD3 and CD43; however, this defect was reversible with the addition of either IL-2, or phorbol myristate acetate (PMA) or anti-CD28 antibodies, Concordantly, the induction of IL-2 (and, in part, IL-3 and IL-4) messenger RNA Vk-as severely reduced in stimulated T cells, but that of other cytokines was either normal (IL-5) or only slightly diminished (interferon-gamma (IFN–γ)). It is concluded that an activation T cell defect exists previous to protein kinase C (PKC) and between membrane receptors and the activation pathway of certain response genes encoding for interleukins involved in proliferation (i.e. lL-2, IL-3 and IL-4), but not of others (i.e. IL-5). The use of T ceil lines from human T lymphocyte activation deficiencies allows dissection of T cell pathology and the corresponding physiological pathways. In the present description, there is an evident independence of the CD28 T cell activation pathway from those induced through CD2 or CD3, and the differential gene regulation of the different interleukins.
Flow cytometry CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication in chronic hepatitis B
Authors: PHAM B-N , MOSNIER J F , WALKER F , NJAPOUM C , BOUGY F , DEGOTT C , ERLINGER S , COHEN J H M , DEGOS F 
Published: July 2010

SUMMARYT lymphocytes have been assumed to play an essential role in tissue injury in patients with chronic hepatitis B. As hepatitis B virus (HBV) is considered as a major factor controlling liver inflammation, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver in accordance with viral replication. Liver-derived lymphocytes and peripheral blood lymphocytes were analysed by flow cytometry in 21 patients with histologically confirmed chronic hepatitis B without cirrhosis. Viral replication was quantified by hybridization of serum HBV DNA. Eleven patients exhibited an active viral replication with serum HBV DNA ranging from 10 to 388pg/ml at the time of the liver biopsy, whereas 10 patients had no detectable serum HBV DNA. In patients exhibiting viral replication. CD4+/CD8+ ratios of liver-derived lymphocytes were significantly higher [P &lt; 005) than those obtained in patients without viral replication. In contrast, the percentage of T cells expressing the γ/δ receptor and that of CD2±/CD57+ cells were similar in both groups of patients. Furthermore, in patients exhibiting viral replication. CD4+/CD8+ ratios of liver-derived lymphocytes correlated with serum HBV DNA levels (P&lt;0.0001). No relationship between CD4+/CD8+ ratio of liver-derived and peripheral blood lymphocytes was observed. Our data indicate that, in patients with chronic hepatitis B. the CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication. This suggests that in situ helper/inducer CD4+ T lymphocytes may positively regulate the cytoxic T cell activity in patients with HBV-related chronic hepatitis.
B7/BB1 provides an important costimulatory signal for CD3-mediated T lymphocyte proliferation in patients with systemic lupus erythematosus (SLE)
Authors: SFIKAKIS P P , OGLESBY R , SFIKAKIS P , TSOKOS G C 
Published: July 2010

SUMMARYSuccessful T cell activation via the T cell receptor (TCR)/CD3 complex requires at least one contact-dependent second signal delivered by costimulatory molecules, including the B7/BB1 molecule, that are present on antigen-presenting cells (APC). SLE is characterized by multiple complex lymphocyte abnormalities of undefined molecular origin. It is currently unclear whether an intrinsic defect of T cell or an underlying APC dysfunction is responsible for defective in vitro proliferation of T cells from patients with SLE. We planned the present experiments to ask whether the TCR/CD3-mediated and B7/BB1-costimulated T cell proliferation is normal in these patients. We used enriched T cell populations that were stimulated with an anti-CD3 MoAb in the presence of controlled quantities of functional B7/BB1 antigen. Freshly isolated T cells from 17 SLE patients (10 and seven patients with either active or inactive disease, respectively) and 11 normal individuals were cocultured with irradiated B7/BB1-transfected P815 cells or parental P815 cells in the presence of OKT3 MoAb at optimal and suboptimal concentrations for 2·5-7 days. Normal or SLE T cells responded similarly to stimulation via anti-CD3, in the absence of B7/BB1 antigen. A several-fold increase in T cell proliferation in the presence of B7/BB1 antigen was observed. Proliferation was inhibited in the presence of anti-B7/BB1 MoAb, but not with control MoAbs. Interestingly, dose-response curves and time kinetics of B7/BB1 costimulation were similar in T cells from patients with either active or inactive SLE at the time of study, and normal individuals. In addition, no differences in the IL-2 receptor release by T cells cultured under these conditions were observed between SLE patients and normal individuals. These results demonstrate that CD28 signalling is not intrinsically impaired in patients with SLE; further studies to investigate whether abnormal B7/BB1 expression is involved in the autoimmune process are needed.
T cell reactivity against antigen 85 but not against the 18- and 65-kD heat shock proteins in the early stages of acquired immunity againstMycobacterium leprae
Authors: LAUNOIS P , N'DIAYE M NIANG , SARTHOU J L , DROWART A , VAN VOOREN J P , CARTEL J L , HUYGEN K 
Published: July 2010

SUMMARYT cell proliferation and interferon-gamma (IFN-γ) production of peripheral blood mononuclear cells (PBMC) from 20 household contacts were tested against the 18- and 65-kD heat shock proteins from Mycobacterium leprae (ML 18 and ML65 respectively) and antigen 85 from Myco. bovis bacille Calmette-Guerin (BCG) (Ag 85) during a 12-months follow-up study. Among the eight contacts that became positive, eight showed positive reactivity against Ag 85, 5/8 against ML65 and 4/8 against ML 18 at the end of the study. Of the 16 contacts who were lepromin-positive either at first or second testing, all responded to Ag 85, 11 to ML 65, but only eight reacted to ML18 antigen. Contacts who were lepromin-positive at first testing developed responses to ML18 only at second testing. In contrast, among the four contacts that remained lepromin-negative during the follow up, three proliferated to Ag 85 either at first or second testing, but only one produced IFN-γ against Ag 85 at the end of the study. These results demonstrated that T cell reactivity and particularly IFN-γ secretion against Ag 85, but not against ML18 and ML65, might be a predominant mechanism in the early stages of acquired protective immunity against Myco. leprae.
Oral and aerosol immunization with viable or inactivatedActinobacillus pleuropneumoniaebacteria: antibody response to capsular polysaccharides in bronchoalveolar lavage fluids (BALF) and sera of pigs
Authors: HENSEL A , PABST R , BUNKA S , PETZOLDT K 
Published: July 2010

SUMMARYTo investigate the antibody response after local application of lung-pathogenic bacteria, pigs were immunized with viable or inactivated Actinohacillus pleuropneumoniae by the oral and aerogenous route. After 3 weeks class-specific immunoglobulins against purified A. pleuropneumoniae capsular polysaccharides (CP) were determined in scrum and BALF by ELISA. A significant increase of IgA antibodies was found in BALF but not in sera of all iminunized pigs. Oral immunization with viable A. pleuropneumoniae and aerosol immunization with either viable or inactivated bacteria resulted in a significant increase of IgG antibodies to the CP antigen in BALF, whereas only aerosol exposure to viable bacteria resulted in a significant increase in IgG antibodies in serum. A significant increase in anti-CP IgM in BALF was observed after aerosol exposure but not after oral immunization. IgM antibodies towards CP increased significantly by both routes of immunization with viable bacteria. The anti-CP activity of all three isotypes in sera and BALF was low in all groups compared with the positive controls, although inoculation of viable A. pleuropneumoniae led to higher levels of antibody concentration than inactivated bacteria. Our results indicate a traffic of primed lymphocytes from the gut into the bronchoalveolar airways and further support the hypothesis that polysaccharide-specific B cells may functionally mature at the mucosal surfaces.
Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria
Authors: JAKOBSEN P H , MORRIS-JONES S , THEANDER T G , HVIID L , HANSEN M B , BENDTZEN K , RIDLEY R G , GREENWOOD B M 
Published: July 2010

SUMMARYPlasma samples from children with mild and severe Plasmodium falciparum malaria and from children with unrelated diseases were collected to investigate whether the clinical outcome of infection was associated with plasma factors which reflected the activity of different cells of the immune system. Children with severe P. falciparum malaria had significantly higher plasma levels of soluble IL-2R than children with mild malaria. Plasma levels of 1L-2R and levels of parasitaemia were significantly correlated. Neither parasitaemia nor plasma levels of tumour necrosis factor-alpha (TNF -a). IL-6. lymphotoxin (LT). interferon-gamma (IFN-γ). IL-4, soluble IL-4R or soluble CD8 differed significantly between the two groups of children with malaria. High plasma levels of soluble CD8 were associated with failure of lymphocytes to produce I FN-γin vitro following stimulation with P. falciparum antigen. We conclude that soluble IL-2R is a useful marker of disease severity independently of the association with levels of parasitaemia, and that functional regulation of different lymphocyte subsets occurs during acute malaria episodes.
Follow up of soluble IL-2 receptor level in metastatic malignant melanoma patients treated by chemoimmunotherapy
Authors: SOUBRANE C L , MOUAWAD R , ICHEN M , SUISSA J , BOREL C H , VUILLEMIN E , BENHAMMOUDA A , BIZZARI J P , WEIL M , KHAYAT D 
Published: July 2010

SUMMARYImmunological parameters following chemoimmunotherapy combination were studied in 31 patients with metastatic malignant melanoina. They received Cisplatni (100 mg/m2) on day 1 and 28, recombinant IL-2 (rIL-2; Eurocetus) in continuous infusion from day 3 to 6, 17 to 21, 31 to 34 and 45 to 49. Interferon-alpha (IFN-α: Roche) was given subcutaneously three times weekly. No significant change in CD4/CD8 ratio at onset or during treatment was observed between responder (n=19) and non-responder (n=12) patients. Regarding the IL-2 receptor (IL-2R) study, the percent age of cells expressing Tac(p55)receptor did not change either for healthy volunteers (n=20) and patients before any therapy, or between responder and non-responder patients. Concerning serum soluble IL-2R shedding before therapy. we observed A significant increase (P=0·001) in patients (79±40 pM) compared with healthy donors (30±15 pM), but no significant variation was seen between responder and non-responder patients. In contrast, during the treatment, the soluble IL-2R level increased in both groups but, interestingly, a significant difference was found between responder and non-responder patients from day 7 (P&lt;0·05) to day 21 (P&lt;0·01), suggesting that the cells from non-responder may be slower in becoming stimulated. This finding is the most striking point of our study and suggests that sIL-2R might be an early predictive factor of the clinical response as obtained by logistic regression (P=0·0063). Therefore patients with a serum soluble IL-2R level greater than 250 pM at day 21 have a 12-fold more chance of undergoing a clinical response.
Expression patterns of Fcγ receptors, HLA-DR and selected adhesion molecules on monocytes from normal and HIV-infected individuals
Authors: Locher CH , Vanham G , Kestens L , Kruger M , Ceuppens J L , Vingerhoets J , Gigase P 
Published: July 2010

SUMMARYThe expression and co-expression profiles of functionally important monocyte surface markers were compared between control and HIV+ individuals using combined physical gating and dim CD4 expression to delineate the monocytes. The FcγRII (CD32), the MHC class II antigen HLADR and the adhesion molecules CDIIa (LFA-1α), CD18 and CD54 (ICAM-1) showed an unimodal distribution. Of these markers, CDI Ia and HLA-DR were up-regulated in the HIV+ subjects compared with controls. The expression levels of the adhesion molecules correlated with each other in both patients and controls. The CD11b (CR3-α), CD14, FcγRI, and FcγRIII markers were bimodally distributed. Compared with controls, monocytes from seropositives contained fewer CDbright+ cells, an equal proportion of FcγIbright+ cells, but twice as many FCγ RIII+ cells. The expression level of FcγRI and CD11b within their brightly positive subset increased as CD4T cells decreased. Both in patients and controls, co-expression of bright CD11b, CD14 and FCγRI was shown, whereas the FcγRIII+ cells were negative or dim positive for the former triad. We conclude that the expression of two FcγR (I and III), of the adhesion molecules CD11a and CD11b and of HLA-DR showed particular alterations on monocytes from HIV+ subjects. The relationship of these phenotypic observations with altered cytokine profiles and altered monocyte function is discussed.
Cytokine production in varicella zoster virus-stimulated limiting dilution lymphocyte cultures
Authors: ZHANG Y , COSYNS M , LEVIN M J , HAYWARD A R 
Published: July 2010

SUMMARYHuman blood lymphocytes were stimulated with varicella zoster virus (VZV) antigen in limiting dilution cultures and the amounts of interferon-gamma (IFN-γ) and IL-4 measured in the supernatants. The results indicate that up to 85% of proliferating cells of young adults produce IFN-γ and up to 10% make IL-4. At limiting dilution, few if any wells were positive for both IFN-γ and IL-4. The amount of IFN-γ per well increased in the presence of antibody to IL-4, but anti-IFN-γ did not increase IL-4 production. The frequency of wells containing IFN-γ was lower in subjects &lt; 19 or &gt; 55 years of age, and the amounts of IFN-γ in positive wells was significantly lower in cultures of the older subjects' lymphocytes. The frequency of IL-4-making cells did not fall significantly with age. The data suggest that the age-related decline in the frequency of blood T cells which responds to VZV affects mainly the cells with a Th1-like cytokine phenotype.
Immunological markers of childhood fevers in an area of intense and perennial malaria transmission
Authors: HURT N , THEIN M , SMITH T , BORDMANN G , GALLATI H , DREES N , TANNER M , WEISS N 
Published: July 2010

SUMMARYIn order to describe presumed paediatric malaria on a cell-immunological basis, the soluble receptors of IL-2 (sIL-2R) and tumour necrosis factor (sTNF-R55 and sTNF-R75) were quantified in highly exposed young Tanzanian children. Sera were obtained from 66 acute and 72 reported febrile patients during health post consultations and follow-ups and from 68 community controls. Levels of sIL-2R, sTNF-R55 and sTNF-R75 were significantly elevated during fever attacks, especially in very young children. Soluble TNF-R75 levels were most stable and those of sTNF-R55 least. Levels of sTNF-R55 were related to the magnitude of fever and thus appeared to reflect attack severity. Levels of sTNF-R75 were highly significantly associated with parasite density, indicating that this response is malaria-specific. The present study indicates that sTNF-R75 levels could become a useful immunological tool in malaria intervention studies, as they reflect changes in malaria-specific immune responses. Future studies should validate this potential in different endemic settings.
Mycobacteria-induced autoantibody production is associated with susceptibility to infection but not with host propensity to develop autoimmune disease
Authors: BRÁS A , ÁGUAS A P 
Published: July 2010

SUMMARYMycobacteria cause increase in autoantibody production in the host during the first weeks of infection. The level of the autoantibody enhancement varies widely in different hosts, suggesting that it depends on features of the host make-up. We have investigated the participation of two characteristics of the host in the modulation of mycobacteria-induced autoantibody production: (i) the host being genetically determined to later develop spontaneous autoimmune disease; (ii) the host being susceptible/resistant to mycobacterial infection. Mycobacterium avium infection was studied in 3-month-old mice that are prone (NZB and C57B1/6-lpr/lpr strains) or not (NZW and C.D2 strains) to develop, when older, autoimmune disease; these murine strains are either naturally susceptible (C57B1/6-lpr/lpr and NZW) or resistant (NZB and C.D2) to mycobacteria. Mycobacterium avium infection was produced by i.p. injection of 3 ± 107 viable bacilli. At days 15 and 30 of the infection, we determined the following parameters; (i) number of cells producing natural autoantibodies (splenic cells showing surface antibodies against bromelain-treated mouse (BrM) erythrocytes); (ii) suppression of the primary response to T cell-dependent antigen (i.e. to sheep erythrocytes); (iii) immunoglobulin classes and IgG isotypes; (iv) titres of anti-dsDNA antibodies; and (v) serum concentrations of interferon-gamma (IFN-γ). We found that the highest elevations in natural autoantibodies were associated with hosts being naturally susceptible to mycobacteria, but not with the host being genetically determined to later develop autoimmune disease. The rise in autoantibodies was predominantly of the IgM type, being associated with suppression of the T cell response and accompanied by increase in serum IFN-γ. Mycobacteria failed to induce any significant enhancement in pathogenic anti-dsDNA antibodies. Our data suggest that the finding of a high level of autoantibodies during the early phase of mycobacterial infection reflects host susceptibility to the infectious agent, and that it is not related with its propensity to later develop autoimmune disorders.
Human neutrophil Fc receptor-mediated adhesion under flow: a hollow fibre model of intravascular arrest
Authors: D'ARRIGO C , CANDAL-COUTO J J , GREER M , VEALE D J , WOOF J M 
Published: July 2010

SUMMARYHuman polymorphonuclear cells (PMN) were found to adhere to a novel model of blood vessel wall-associated IgG. The internal surfaces of cellulose acetate hollow fibres, of comparable internal diameter to small blood vessels, were coated with normal serum human IgG, heat-aggregated IgG (HAIgG), laminin or fibrinogen. Under conditions of flow mimicking those in a small vessel. PMN were found to adhere markedly only to immunoglobulin-coated fibres. Arrest on HAIgG was inhibited by excess soluble IgG but not by bovine serum albumin (BSA), demonstrating that the adhesion was IgG-specific and presumably mediated by FcγR on the PMN surface. Pre-adsorption of serum components onto HAIgG-coated fibres enhanced PMN arrest, due most probably to fixation of complement components by immobilized HAIgG, resulting in additional potential to entrap PMN via complement receptors such as CR3. Treatment of PMN with the regulatory neuropeptide substance P also enhanced adhesion to HAIgG-coated fibres and caused increased surface expression of FcγRI, FcγRII and FcγRIII. A mouse cell line derived from L cells, hR4C6, stably transfected with human FcγRII, was found to adhere under flow lo HAIgG-coated fibres, whilst untransfected parent L cells did not. This adhesion was similarly inhibited by excess soluble IgG, confirming the capability of FcγR to mediate cell arrest. The study strongly suggests that FcγR may play an important role in intravascular PMN arrest and we speculate that in inflammatory diseases PMN may adhere via FcγR to immobilized immunoglobulin on the vascular endothelium, with subsequent degranulation and tissue damage.
Spontaneous production of various cytokines except IL-4 from CD4+ T cells in the affected organs of sarcoidosis patients
Authors: Hoshino T , Itoh K , Gouhara R , Yamada A , Tanaka Y , Ichikawa Y , Azuma M , Mochizuki M , Oizumi K 
Published: July 2010

SUMMARYWe investigated surface antigens and spontaneous cytokine production of T cells from broncho-alveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary sarcoidosis patients for a better understanding of the role of T cells in granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on freshly isolated T cells in the BALF of patients were significantly lower than those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or healthy donors (HD). In contrast, the levels of CD80 (B7/B7-1) and CD86 (B70/B7-2) antigen expression were significantly higher on these T cells and alveolar macrophages in the BALF of patients. Fifty-three T cell clones (TCC) established from the BALF and AH of the three sarcoidosis patients displayed primarily either CD4+ CD11b+ CD28+ or CD4+ CD11b- CD28- phenotypes. Most (61–90%) of these TCC spontaneously produced greater amounts of IL-1a, IL-10, tumour necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) than did TCC from the PBL from sarcoidosis patients or HD (P &lt; 0·05). Interferon-gamma (IFN-γ), IL-6, and IL-2, but not IL-4, were also produced by 40–48% of these TCC. These results suggest that CD4+ T cells of the affected organs of sarcoidosis patients are activated and involved in the immunopathogenesis of sarcoidosis through production of various cytokines.