bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma
Authors: VAN DEN HOVE L E , VAN GOOL S W , VAN POPPEL H , BAERT L , COOREVITS L , VAN DAMME B , CEUPPENS J L 
Published: November 2003

SUMMARY
We investigated the phenotype and functional capacities of tumour-infiltrating lymphocytes (TIL), freshly isolated from primary renal cell carcinoma (RCC) specimens (n = 20). Three-colour flow cytometry immunophenotyping revealed that RCC TIL consist mainly of CD3+ T cells, with a clear predominance of CD4−CD8+ over CD4+ CD8− T cells, and a marked population of CD4+ CD8+ T cells. Natural killer (NK) cells were also strongly represented (&gt; 25% in 15 of 20 tumour samples), while B cells constituted a minor TIL subset (&lt; 5% in 18 of 20 tumour samples). More importantly, the T and NK cells within the tumour displayed a significantly higher expression of the early activation marker CD69 than their counterparts in adjacent normal renal tissue and in peripheral blood. Expression of CD54 and of HLA-DR was also elevated on CD3+ TIL, and HLA-DR expression was further vigorously up-regulated following ex vivo stimulation with anti-CD3, all suggesting enhanced immune activity within the tumour microenvironment. CD3+ CD4+ TIL displayed a normal capacity to up-regulate CD25 expression and to secrete both Th1-type (IL-2, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) and Th2-type (IL-4, IL-5 and IL-10) cytokines upon triggering with anti-CD3. Furthermore, cytokine production was susceptible to modulation by CD28 costimulation. CD3+ CD8+ TIL, on the other hand, consistently demonstrated a poor up-regulation of CD25 upon triggering with anti-CD3, and displayed poor ex vivo cytolytic activity in an anti-CD3-redirected 4-h cytotoxicity assay against murine P815 cells. Collectively, our findings indicate that the CD3+ CD4+ TIL in RCC have normal functional capacities, whereas the proportionally major CD3+ CD8+ TIL are functionally impaired. The relevance of these findings to the in vivo local immune response in RCC is discussed.
Immunoprecipitation of melanogenic enzyme autoantigens with vitiligo sera: evidence for cross-reactive autoantibodies to tyrosinase and tyrosinase-related protein-2 (TRP-2)
Authors: KEMP E H , GAWKRODGER D J , WATSON P F , WEETMAN A P 
Published: November 2003

SUMMARY
In the present study we describe the detection of TRP-2 antibodies in vitiligo patients using in vitro35S-labelled human TRP-2 in a radioimmunoassay. Of 53 vitiligo sera examined in the assay, three (5.9%) were found to be positive for TRP-2 antibodies. In contrast, 20 control sera, sera from 10 patients with Hashimoto's thyroiditis and sera from 10 patients with Graves' disease were all negative. All three patients positive for TRP-2 antibodies (mean age 54 years, age range 50–63 years) had had vitiligo of the symmetrical type for more than 1 year and all of them also had an associated autoimmune disorder: Graves' disease in one and autoimmune hypothyroidism in two. In addition, antibodies to the melanogenic enzyme tyrosinase were present in their serum. To examine any immunological cross-reactivity between TRP-2 and tyrosinase, the three vitiligo sera positive for TRP-2 antibodies were preabsorbed with COS-7 cell extract containing either expressed TRP-2 or tyrosinase, and subsequently used in the radioimmunoassay. These absorption studies indicated that preincubation with both proteins inhibited the immunoreactivity of the positive sera in the immunoassay using in vitro translated 35S-TRP-2. This antibody cross-reactivity suggests the humoral response to the two melanogenic enzymes in these patients may not be entirely independent.
Characterization of fertilization-blocking monoclonal antibody 1G12 with human sperm-immobilizing activity
Authors: KOMORI S , KAMEDA K , SAKATA K , HASEGAWA A , TOJI H , TSUJI Y , SHIBAHARA H , KOYAMA K , ISOJIMA S 
Published: November 2003

SUMMARY
A mouse hybridoma (1G12) producing sperm-immobilizing MoAb to human sperm was established and characterized in order to study the antigens relevant to sperm immobilization by antibodies. MoAb 1G12 had strong sperm-immobilizing and agglutinating activities and also showed a fertilization-blocking activity on in vitro fertilization tests. The antibody absorption experiments showed that MoAb 1G12 reacted not only to ejaculated sperm but also human seminal plasma, suggesting that the corresponding antigen might be a sperm coating antigen. The MoAb also reacted with peripheral blood lymphocytes. In histochemical studies, the epithelia of corpus epididymis were most strongly stained. Ejaculated sperm were stained with a granular pattern for their entire surface by immunofluorescence. MoAb 1G12 recognized polymorphic glycoproteins of 15–25 kD in the ejaculated sperm extract in Western blot analysis. After deglycosilation of the sperm extract, only a single staining band of under 15 kD was detected by MoAb 1G12. This suggests that the antigen epitope recognized by MoAb 1G12 might be a peptide of the core portion of the glycoprotein. MoAb 1G12 might be a useful tool for studying the mechanism of egg–sperm interaction, and also be applied to identifying the corresponding antigen by using gene technology.
Sex and parity modulate cytokine production during murine ageing
Authors: BARRAT F , LESOURD B , BOULOUIS H-J , THIBAULT D , VINCENT-NAULLEAU S , GJATA B , LOUISE A , NEWAY T , PILET Ch 
Published: November 2003

SUMMARY
We have previously shown that physiological hormone differences related to pregnancy or sex affect the age-related distribution of mononuclear cell populations during murine ageing. To determine whether such changes are involved in the age-related changes in functions of T cells, we examined the secretion of major T cell immunoregulatory cytokines (IL-2, IL-4, interferon-gamma (IFN-γ), IL-3, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) of in vitro concanavalin A-activated spleen cells of C57Bl/6 mice. The study included multiparous and virgin females and males at 2, 8, 15 and 23 months of age. Short-term effects of parity (8 months) were evidenced by the decrease of IFN-γ and the preserved IL-2 production in multiparous females (8 months), while IFN-γ was unchanged and IL-2 decreased in virgin mice. The increase in IL-4 production appeared earlier in multiparous females (15 months) than in virgin mice (23 months). The increase in IL-4/IFN-γ and IL-4/IL-2 ratios at 8 and 15 months, respectively, in multiparous females, suggests that pregnancy modifies the Th1/Th2 equilibrium. In late adulthood (15 months), IL-6 and GM-CSF production was higher in multiparous females than in virgin males or females. Sex differences were also noticed: IFN-γ secretion capacity was lower in males than in females during ageing. This study underlines that the onset, magnitude and kinetics of the age-related changes in cytokine production are parity- and sex-dependent. These changes probably influence the incidence of age-related diseases and may explain the greater longevity of females.
Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization
Authors: TZIOUFAS A G , YIANNAKI E , SAKARELLOS-DAITSIOTIS M , ROUTSIAS J G , SAKARELLOS C , MOUTSOPOULOS H M 
Published: November 2003

SUMMARY
The B cell epitope mapping of La/SSB was performed using 20 mer synthetic peptides overlapping by eight amino acids covering the whole sequence of the protein. IgG, purified from sera of five patients with systemic lupus erythematosus (SLE) and four sera from patients with primary Sjögren's syndrome (pSS) were tested against the overlapping synthetic peptides. Peptides highly reactive with purified IgG were those spanning the regions 145–164, 289–308, 301–320 and 349–368 of the La protein. Determination of the minimum required length of the antigenic determinants disclosed the following epitopes:147HKAFKGSI154, 291NGNLQLRNKEVT302, 301VTWEVLEGEVEKEALKKI318 and 349GSGKGKVQFQGKKTKF364. Predicted features and molecular similarities of the defined epitopes were investigated using protein databases. The La epitope 147HKAFKGSI154 presented 83.3% similarity with the 139HKGFKGVD146 region of human myelin basic protein (MBP) and 72% similarity with the fragment YKNFKGTI of human DNA topoisomerase II. Peptides corresponding to these sequences cross-reacted with anti-La/SSB antibodies. Sixty-three sera with anti-La/SSB antibodies from patients with pSS or SLE, 35 sera without anti-La/SSB antibodies from patients with SS or SLE and 41 sera from age/sex-matched healthy blood donors were tested against biotinylated synthetic epitope analogues in order to determine their sensitivity and specificity for the detection of anti-La/SSB antibodies. Anti-La/SSB were detected with various frequencies ranging from 20% to epitope 147HKAFKGSI154 to 100% to epitope 349GSGKGKVQGKKTKF364. The overall sensitivity and specificity using all assays with the synthetic peptides were found to be 93.6% and 85.6%, respectively. In conclusion, antibodies to La/SSB constitute a heterogeneous population, directed against different linear B cell epitopes of the molecule. The epitope 147HKAFKGSI154 presents molecular similarity with fragments of two other autoantigens, i.e. human MBP and DNA topoisomerase II. Finally, synthetic epitope analogues exhibit high sensitivity and specificity for the detection of anti-La/SSB antibodies.
Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1
Authors: KIM J H , LOVELAND J E , SITZ K V , RATTO KIM S , MCLINDEN R J , TENCER K , DAVIS K , BURKE D S , BOSWELL R N , REDFIELD R R , BIRX D L 
Published: November 2003

SUMMARY
The failure of immune effector mechanisms to control HIV-1 infection has important consequences for the human host. In a randomized cohort of HIV-infected patients, there was striking in vitro restriction of the proliferative response to HIV-1 envelope protein (Env), gp160; only 34% of patients recognized Env. Therapeutic vaccination with recombinant gp160 or gp120 (rgp160, rgp120) reversed the restriction in vitro, with Env recognition rising to 81%. Peripheral blood mononuclear cells (PBMC) from HIV-infected vaccine recipients, placebo recipients, and seronegative volunteers were cultured with exogenous IL-7 or IL-12 and either tetanus toxoid (TT) or gp160. IL-7 significantly augmented proliferative responses to TT and gp160, whereas IL-12 only affected proliferation to gp160. IL-7, but not IL-12, increased the number of HIV-infected placebo recipients who recognized rgp160. IL-12 had its greatest effect in the induction of rgp160-specific responses from seronegative individuals. The data suggest that these two cytokines have differential activity in the relief of restricted cellular immunity to Env; the predominant effect of IL-7 is in individuals who have been primed by exposure to antigen, while the effect of IL-12 is most evident in seronegative, unprimed individuals. Modification of restricted proliferative responses to Env by vaccination or cytokines in vitro suggests that strategies incorporating IL-7 or IL-12 as adjuvants may selectively boost cellular reactivity to HIV-1.
IL-12 inhibits in vitro immunoglobulin production by human lupus peripheral blood mononuclear cells (PBMC)
Authors: HOUSSIAU F A , MASCART-LEMONE F , STEVENS M , LIBIN M , DEVOGELAER J-P , GOLDMAN M , RENAULD J-C 
Published: November 2003

SUMMARY
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by polyclonal B cell activation and by the production of anti-double-stranded (ds) DNA antibodies. Given the inhibitory effects of IL-12 on humoral immune responses, we investigated whether IL-12 displayed such an activity on in vitro immunoglobulin production by SLE PBMC. Spontaneous IgG, IgG1, IgG2, IgG3 and IgM antibody production was dramatically reduced by addition of IL-12. These results were confirmed by Elispot assays detecting IgG- and anti-dsDNA-secreting cells. While IL-6 and TNF titres measured in PBMC supernatants were not modified by addition of IL-12, interferon-gamma (IFN-γ) titres were up-regulated and IL-10 production down-regulated. Since addition of IFN-γ did not down-regulate immunoglobulin production and since the inhibitory activity of IL-12 on immunoglobulin synthesis was not suppressed by anti-IFN-γ antibody, we concluded that the effect of IL-12 on immunoglobulin production was not mediated through IFN-γ. Our data also argue against the possibility that down-regulation of endogenous IL-10 production was responsible for the effect of IL-12. Thus, inhibition of IL-10 production by IFN-γ was not accompanied by inhibition of immunoglobulin production, and conversely, restoration of IL-10 production by anti-IFN-γ antibody did not suppress the inhibitory activity exerted by IL-12 on immunoglobulin production. Taken together, our data indicate that reduction of excessive immunoglobulin and anti-dsDNA antibody production by lupus PBMC can be achieved in vitro by IL-12, independently of IFN-γ and IL-10 modulation.
Increased levels of IL-13 mRNA, but not IL-4 mRNA, are found in vivo in peripheral blood mononuclear cells (PBMC) of patients with atopic dermatitis (AD)
Authors: KATAGIRI K , ITAMI S , HATANO Y , TAKAYASU S 
Published: November 2003

SUMMARY
Previous studies using in vitro systems with various stimuli have shown that PBMC from patients with AD show increased levels of IL-4 but decreased levels of interferon-gamma (IFN-γ) compared with PBMC from normal controls. However, in vitro conditions do not always mimic the in vivo condition. We therefore believe that it is important to quantify the expression of these cytokines in freshly isolated PBMC. This study examines the expression of IFN-γ, IL-4 and IL-13 mRNA in freshly isolated PBMC from adult patients with AD, from patients with psoriasis vulgaris and from healthy adults, using the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Levels of IFN-γ mRNA were significantly lower in PBMC of patients with AD than in controls. IL-4 mRNA levels did not differ significantly between groups. Conversely, levels of mRNA for IL-13 were significantly greater in PBMC of patients with AD than in controls. An increase in IL-13 expression may regulate the in vivo synthesis of IgE in patients with AD.
Intravenous immunoglobulin (IVIG) treatment of experimental colitis induced by dextran sulfate sodium in rats
Authors: SHINTANI N , NAKAJIMA T , NAKAKUBO H , NAGAI H , KAGITANI Y , TAKIZAWA H , ASAKURA H 
Published: November 2003

SUMMARY
We investigated the therapeutic effect and immunological action mechanism of IgG in experimental colitis induced by 3% dextran sulfate sodium in rats. Intravenous injection of homologous (rat) IgG (400 mg/kg per day) caused a significant suppression of occult blood discharge and ulcerative lesions in the colon, while no suppressive effect was observed in the case of heterologous (human) IgG. The positive effect of rat IgG on the lesions was also clearly shown by the histological examinations. Generation of proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α) and IL-1α, in the lesions was found to be inhibited by administration of rat IgG. Little or no suppressive action was exerted by human IgG. Careful examination of recruited T cells and macrophages, both of which are thought to play important roles in the development of ulcerative colitis, indicated that rat IgG, but not its human counterpart, decreased the number of immunocompetent cells in colonic mucosa. Meanwhile, in an in vitro study, both forms of IgG were shown to suppress production of TNF-α and IL-1α from lamina propria mononuclear cells isolated from rat colon. These findings suggest that, mainly by suppressing recruitment of immunocompetent cells into the lesions, homologous IgG may reduce the occurrence of colitis.
Defective antigen presentation by lavage cells from terminal patients with cystic fibrosis
Authors: KNIGHT R A , KOLLNBERGER S , MADDEN B , YACOUB M , HODSON M E 
Published: November 2003

SUMMARY
Macrophages separated from lavage samples obtained from lungs removed at transplantation from patients with cystic fibrosis (CF) and other lung diseases, have been compared with circulating monocytes from the same patients for their ability to stimulate allogeneic normal circulating lymphocytes and to present antigen to autologous hilar lymph node cells. In general, macrophages separated from lavage samples from CF patients were unable to stimulate allogeneic lymphocytes and to present antigen, although monocytes from the same patients were functional in both assays. In contrast, lavage cells from non-CF patients were generally effective in both allogeneic stimulation and antigen presentation. These data suggest that immune cells within the lungs of CF patients are functionally compromised, a deficiency which may contribute to the recurrent infections characteristic of the disease.
Effect of immunoglobulin therapy on phagocytosis by polymorphonuclear leucocytes in whole blood of neonates
Authors: FUJIWARA T , TANIUCHI S , HATTORI K , KOBAYASHI T , KINOSHITA Y , KOBAYASHI Y 
Published: November 2003

SUMMARY
There has been some disagreement as to the clinical effect of intravenous immunoglobulin (IVIG) therapy on neonatal bacterial infections. We therefore evaluated the effect of IVIG therapy on neonatal polymorphonuclear leucocyte (PMN) functions by monitoring phagocytosis and hydrogen peroxide (H2O2) production. Subjects were 10 mature neonates who had normal plasma levels (i.e. equal to adult plasma levels) of IgG and nine premature neonates who had lower plasma levels of IgG. Phagocytosis by PMN was measured using flow cytometric analysis of whole blood. Addition of γ-globulin to the whole blood of mature neonates increased phagocytosis, but not significantly. Higher doses of added γ-globulin (&gt; 2·0 mg/ml, the concentration was expressed as that in the final reaction volume) decreased phagocytosis to under baseline level. In premature neonates addition of γ-globulin increased phagocytosis and the significant maximum effect was observed with 0·5 mg/ml of the additional γ-globulin. Higher doses of additional γ-globulin (2·5 mg/ml) decreased phagocytosis to baseline level. Phagocytosis in four mature and four premature neonates was compared before and after 1 g/kg of IVIG therapy. Phagocytosis in mature neonates after IVIG therapy did not change compared with the pretreatment level. On the other hand, phagocytosis in premature neonates after IVIG therapy significantly increased compared with its pretreatment level. In both mature and premature neonates H2O2 production following phagocytosis varied in parallel with changes of phagocytosis. The patterns of H2O2 production following phagocytosis were essentially similar to those observed with phagocytosis. The above results are expected to form the basis for a rational indication for IVIG therapy against bacterial infections in neonates with low plasma IgG levels.
Regulation of endotoxin-induced IL-6 production in liver sinusoidal endothelial cells and Kupffer cells by IL-10
Authors: KNOLLE P A , LÖSER E , PROTZER U , DUCHMANN R , SCHMITT E , ZUM BÜSCHENFELDE K-H M , ROSE-JOHN S , GERKEN G 
Published: November 2003

SUMMARY
Sinusoidal endothelial cells and Kupffer cells are the first cell populations in the liver that come into contact with gut-derived endotoxin in portal blood. Although endotoxin concentrations as high as 1 ng/ml are physiologically present in portal blood, no local inflammation is seen. We show that the proinflammatory cytokine IL-6, which is central to the development of inflammatory reactions in the liver, is produced by sinusoidal endothelial cells and Kupffer cells in response to low concentrations of endotoxin (100 pg/ml to 1 ng/ml). The anti-inflammatory cytokine IL-10 down-regulated endotoxin-induced IL-6 release in endothelial and Kupffer cells. Importantly, Kupffer cells secreted IL-10 after endotoxin stimulation and may therefore participate in the local regulation of inflammation. We have found that IL-6 secretion in Kupffer cells is tightly regulated by endogenous IL-10, because increased IL-6 secretion resulted when neutralizing antibodies to IL-10 were added to resting and endotoxin-challenged Kupffer cells. Furthermore, repeated exposure of endothelial cells to endotoxin induced a state of tolerance which resulted in decreased release of IL-6 in response to a second endotoxin challenge. Our results support the notion that inflammatory reactions in the liver in response to endotoxin are down-regulated by local release of the anti-inflammatory cytokine IL-10 that is produced by Kupffer cells.
CD8+ T cells and not CD4+ T cells are hyporesponsive to CD28- and CD40L-mediated activation in HIV-infected subjects
Authors: VINGERHOETS J , KESTENS L , PENNE G , DE VUYST H , VANDENBRUAENE M , PELGROM Y , BOSMANS E , DE BOER M , KASRAN A , AZUMA M , COLEBUNDERS R , CEUPPENS J L , VANHAM G 
Published: November 2003

SUMMARY
T cell dysfunction in HIV-infected subjects could be the consequence of altered sensitivity of CD4+ or CD8+ T cells to various costimulatory signals. Therefore, we studied proliferation and cytokine production in highly purified CD8+ and CD4+ T cells from HIV-infected and HIV− subjects, induced by co-activation via cell-bound CD80, CD86 and CD40 or by allo-activation. Regardless of the nature of the first and the costimulatory signal, CD8+ T cells from patients proliferated consistently less than controls, while responses from CD4+ T cells were similar in patients and controls. This phenomenon was observed after ligation of CD28 combined with anti-CD3 or phorbol myristate acetate (PMA), but also after allogeneic stimulation and after activation by CD40 and anti-CD3. Anti-CD3 combined with CD80 or CD86 induced a mixed Th1/Th2-type cytokine profile in both CD4+ and CD8+ T cells from controls, whereas anti-CD3 plus CD40 induced only low levels of Th2-type cytokines and no interferon-gamma (IFN-γ) in CD4+ T cells. Compared with controls, CD4+ T cells from patients produced slightly lower levels of IL-10 but equal amounts of IFN-γ, IL-4 and IL-5, while CD8+ T cells from patients produced less of all cytokines tested. In conclusion, responses of purified CD4+ T cells from HIV+ subjects to various costimulatory pathways are relatively intact, whereas CD8+ T cells are hyporesponsive at the level of proliferation and cytokine production. A generalized intrinsic CD8+ T cell failure might contribute to viral and neoplastic complications of HIV infection.
Establishment and characterization of cloned CD4− CD8−αβ-T cell receptor (TCR)-bearing autoreactive T cells from autoimmune NZB×NZW F1 mice
Authors: CHEN Y-C , YE Y-L , CHIANG B-L 
Published: November 2003

SUMMARY
Murine models such as NZB/W F1, NZB.H-2bm12 and MRL.lpr/lpr mice have provided greater insight into the pathogenic mechanisms of lupus. To understand further the roles of T cells and cytokines in the pathogenesis of murine lupus, 11 cloned anti-DNA antibodies augmenting autoreactive T cell lines were derived from NZB/W F1 mice. All these autoreactive cells responded to syngeneic splenic cells and helped syngeneic B cells to produce anti-DNA antibodies, especially the IgG antibody. Ten out of 11 autoreactive T cell lines expressed neither CD4 nor CD8 cell surface markers on their surface. In addition, the cytokine production pattern of these autoreactive T cell lines was predominantly of type 0 (Th0) or type 2 T helper cells (Th2). To further investigate the role of accessory molecules in the activation of these autoreactive T cell lines, expression of IL-2R and heat-stable antigen (HSA) on these autoreactive T cells was analysed. Results suggest that the HSA played a critical role in the activation and function of these double-negative cloned autoreactive T cells.