bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose exposure to antigen induces sub-clinical sensitization
Authors: FRIEDMANN P S , REES J , WHITE S I , MATTHEWS J N S 
Published: July 2010

SUMMARY
We examined the effects of a small initial sensitizing dose of antigen (dinitrochlorobenzene, DNCB) on the subsequent response to a second, defined sensitizing stimulus. The second stimulus was actually the regimen of four doses of DNCB (3.125, 6.25, 12.5, and 25 μg; total 46.9 μg) normally used as the elicitation challenge. In two separate experiments 13 and 18 control subjects received an initial ‘challenge’ with the four doses to induce sensitivity, and 4 weeks later their responses were determined with a second, elicitation challenge. Two groups of 12 and 15 experimental subjects received an inital dose predicted to induce clinically detectable sensitivity in 50% or 25%, respectively. Four weeks later, their responsiveness was determined with quantitative challenge and the subjects who gave no response received a further challenge 4 weeks later. Their responses, compared with those from the control subjects, were augmented, indicating that sub-clinical priming of the immune system had indeed occurred.
Intra-epithelial lymphocytes: interferon-gamma production and suppressor/cytotoxic activities
Authors: EBERT E C 
Published: July 2010

SUMMARYHuman intraepithelial lymphocytes (IEL) proliferate minimally in response to phytohaemagglutinin (PHA), but produce as much interleukin-2 (IL-2) as do peripheral blood lymphocytes (PBL). The addition of sheep erythrocytes during activation of IEL with PHA markedly augments both T cell functions. This study evaluates the ability of IEL to produce interferon-gamma (IFN-γ) and to develop suppressor and cytotoxic activities when stimulated with mitogens in the presence or absence of sheep erythrocytes. PHA-activated IEL produced as much IFN-γ as did PHA-activated peripheral blood CD8+ T lymphocytes. IEL activated by concanavalin A (Con A) demonstrated less suppressor activity directed against T cell proliferation than did Con A-activated peripheral blood CD8+ T lymphocytes. IEL generated less mitogen-induced cellular cytotoxicity and lymphokine-activated killer cell activity than did peripheral blood CD8+ T lymphocytes. The addition of sheep erythrocyte lysates during mitogen stimulation of IEL markedly enhanced their proliferation and lymphokine production but did not affect their suppressor or cytotoxic activities.
Macrophage activation in falciparum malaria as measured by neopterin and interferon-gamma
Authors: BROWN A E , WEBSTER H K , TEJA-ISAVADHARM P , KEERATITHAKUL D 
Published: July 2010

SUMMARY
Macrophage activation during acute falciparum malaria in 71 Thai adults was investigated by measuring urinary neopterin and serum interferon-gamma (IFN-γ). Neopterin, a product of IFN-γ-activated macrophages, was elevated in 94% of patients upon admission (day 0, prior to treatment) and in all at some time during the period of study. Neopterin levels tended to rise further (days 1–5) before falling back towards the normal range as patients recovered following effective chemotherapy (days 6–8). IFN-γ was measured in 32 patients and found to be directly related to neopterin concentration. Both neopterin and IFN-γ values were highest in patients experiencing a first malaria infection. Among those with histories of prior malaria, neopterin and IFN-γ levels were inversely related to the number of previous infections. Morbidity, as assessed by degree and duration of fever, was directly related to neopterin concentration. This longitudinal study quantitatively describes the extent and duration of macrophage activation in falciparum malaria. The data also suggest that with repeated malaria infection and antigen exposure, there is a progressive decrease or possibly suppression of the T cell-macrophage interaction mediated by IFN-γ.
Induction and increase of HLA-DR antigen expression by immune interferon on ML-3 cell line enhances the anti-HLA-DR immunotoxin activity
Authors: CHIRON M , JAFFREZOU J P , CARAYON P , BORDIER C , ROUBINET F , XAVIER C , BRANDELY M , LAURENT G 
Published: July 2010

SUMMARYIn order to evaluate the impact of induction and increase target antigen expression on immunotoxin potency, we measured the potentiating effect of recombinant immune interferon-gamma (rIFN-γ) on the cytotoxicity of an anti HLA-DR ricin A-chain immunotoxin (2G5 RTA-IT) on the myeloid cell line ML-3. After 48 h of incubation with rIFN-γ (500 U/ml) the percentage of 2G5-positive cells increased from 40%. to 79%, and the 2G5 mean density was enhanced by 10-fold (11000 versus 110 000 molecules/cell). Concurrently, rIFN-γ pretreatment induced a dramatic improvement of 2G5 RTA-IT dose-effect cytotoxicity, as well as immunotoxin cytotoxicity kinetics. When 2G5 RTA-IT was used at the optimal dose of 10-8m (the maximum dose which avoided non-specific ricin A-chain cytotoxicity), the immunotoxin-induced cell kill increased with the percentage of DR-positive ML-3 cells according to a similar linear-logarithmic function of rIFN-γ concentration. Moreover, in the same range of rIFN-γ concentrations, the killing values and the percentage of DR-positive M L-3 cells were similar if not identical. These findings imply that the enhancement of 2G5 RTA-IT cytotoxicity by rIFN-γ is mainly related to the rIFN-y 2G5 antigen induction on HLA-DR negative cells when immunotoxin was used at 10-8m. Furthermore. 2G5 RTA-IT dose effect cytotoxicity on DR-expressing ML-3 cells, when used at lower concentrations, was also increased by rIFN-y in a dose-dependent manner. This result suggests that for immunotoxin concentrations close to the limiting membrane saturation dose (10-10 M). rIFN-y may not solely act by inducing HLA-DR expression on DR-negative ML-3 subpopulation but also by increasing individual cellular DR density on DR expressing ML-3 cells. Finally, our study showed that immunotoxin potency on malignant cell populations which display an heterogeneous antigen expression, could be greatly improved by the use of rIFN-γ.
Diverse target antigens recognized by circulating antibodies in anti-neutrophil cytoplasm antibody-associated renal vasculitides
Authors: SAVIGE J A , GALLICCHIO M , GEORGIOU T , DAVIES D J 
Published: July 2010

SUMMARY
Antibodies that arc directed against cytoplasmic constituents of neutrophils and monocytes (anti-neutrophil cytoplasm antibodies, ANCA) have been described in Wegener's granulomatosis, microscopic polyarteritis (MPA) and some cases of segmental necrotizing glomerulonephritis (SNGN). Other antibodies occasionally described in Wegener's granulomatosis and MPA include anti-nuclear antibodies (ANA) and anti-glomerular basement membrane (GBM) antibodies. We have studied the diversity of the corresponding antigens in ANCA-associated renal diseases. Sera from 46 patients with active histologically proven Wegener's granulomatosis, MPA and SNGN were tested for ANCA by indirect immunofluorescent examination of normal peripheral blood neutrophils. Thirty-four sera (74%) were positive; 16 were associated with diffuse cytoplasmic staining (cANCA) and 18 with perinuclear staining (pANCA). In addition, five demonstrated antineutrophil-specific nuclear staining (ANNA). On Western blotting of the neutrophil extract, five sera recognized a 29-kD molecule recently identified as neutrophil proteinase 3. Two sera with typical cANCA bound to molecules of 36, 38 and 116 kD and another to a molecule of 22 kD. The final serum associated with pANCA bound to a molecule of about 12 kD. Thirteen sera out of 46 (28%) tested in an ELISA contained anti-myeloperoxidase antibodies; 10 of these were associated with pANCA and two others with ANNA. Three sera of 17 (18%) tested contained anti-elastase antibodies; these also contained anti-myeloperoxidase antibodies and were associated with pANCA. However, eight sera with pANCA were negative for anti-myeloperoxidase antibodies and three of these were also negative for anti-elastase antibodies, suggesting further unidentified target antigen or antigens associated with the pANCA. Fifteen of the 34 sera positive for ANCA also demonstrated anti-nuclear staining on Hep-2 cells (53%) in a speckled, homogeneous, or nucleolar pattern. ANA were significantly associated with the presence of pANCA (P &lt; 0.01), and levels of ANA and ANCA fell in parallel after treatment. One serum with a pANCA was also positive for anti-GBM antibodies. Inhibition studies using ELISAs for anti-GBM antibodies indicated that there was no cross-reactivity between target molecules recognized by these antibodies. The diversity of target molecules recognized by ANCA suggests that cross-reactivity with bacterial structures is less likely as the primary aetiological event in the development of these antibodies than tissue destruction; and that cross-reactivity with vascular endothelium is also unlikely as the pathogenetic basis of vessel disease.
Occurrence of two germline-related rheumatoid factor idiotypes in rheumatoid arthritis and in non-rheumatoid seropositive individuals
Authors: KOURI T , CROWLEY J , AHO K , PALOSUO T , ISOMÄKI H , VON ESSEN R , HELIÖVAARA M , CARSON D , VAUGHAN J H 
Published: July 2010

SUMMARYHuman rheumatoid factor (RF) paraproteins express two distinct light chain cross-reactive idiotypes defined by the monoclonal antibodies 17.109 and 6B6.6. These germline gene-related cross-reactive idiotypes are both carried on Vk3 light chains and are each present on about one-third of IgM RF paraproteins. We assessed the degree to which these idiotypes are represented in polyclonal RFs. We used rheumatoid arthritis (RA) and non-RA RF-positive sera selected from a large cross-sectional population study (the Mini-Finland Health Survey), and sera from a community-based follow-up study of recent-onset RA patients from Heinola, Finland. In the Mini-Finland Health Survey, elevated levels of the 17.109 RF idiotype were seen in sera of 13% of the RA and 19% of the non-RA group; 6B6.6 RF was seen in 26% of the RA and 28% of the non-RA group. In sera of the Heinola follow-up study, 17.109 RF was seen in 12% initially, but in only 3% at 8 years. Similarly, 6B6.6 RF was detected in 25% initially, but in only 7% at 8 years. Ten sera positive for RF prior to the onset of clinical RA were identified from individuals of a second large population study from Finland (North Karelia project); two of these sera exhibited the 6B6.6 idiotype; none exhibited the 17.109 idiotype. The data are consistent with the concept that these germline gene-related cross-reactive RF idiotypes occur frequently in the polyclonal RF of non-RA as well as RA sera, and that in RA the idiotypes may sometimes be reduced or lost as a consequence of somatic diversification of the RF through somatic mutation, usage of new germline genes, or both.
Adjuvant-induced arthritis in rats. Evidence that autoimmunity to homologous collagens types I, II, IX and XI is not involved in the pathogenesis of arthritis
Authors: CREMER M A , TOWNES A S , KANG A H 
Published: July 2010

SUMMARYWe examined the sera of arthritic outbred Wistar and Sprague-Dawley rats and inbred Fisher 344 and Wistar-Lewis rats for autoantibodies to rat type I, II, IX and XI collagens following the induction of arthritis with mycobacteria (MTB). Although many sera collected over an extended time were assayed in addition to acid eluates of arthritic joints, convincing evidence for autoimmunity to collagen could not be demonstrated. Instead, modest non-specific reactions were observed to collagen, irrelevant proteins, and buffer-treated plastic microtitre wells. In contrast, antibodies to purified protein derivative (PPD) were detected in the sera of rats developing adjuvant-induced arthritis, and antibodies to type II collagen, in the sera and joint eluatc of rats developing experimental collagen-induced arthritis. Lastly. delayed-type hypersensitivity responses to collagen could not be detected, nor could adjuvant-induced arthritis be attenuated by soluble collagen injected intravenously before challenge with MTB. We conclude that adjuvant-induced arthritis and experimental collagen-induced arthritis are distinct models of rheumatic disease and that autoimmunity to collagen is neither prevalent in adjuvant-induced arthritis nor necessary for its pathogenesis.
Anomalous expression of HLA class II molecules on keratinocytes and fibroblasts in hypertrophic scars consequent to thermal injury
Authors: CASTAGNOLI C , STELLA M , MAGLIACANI G , ALASIA S TEICH , RICHIARDI P 
Published: July 2010

SUMMARY
Immunoperoxidase staining of skin sections obtained from 11 hypertrophic scars, six normotrophic scars and three samples of normal skin were performed using anti-HLA monoclonal antibodies (HLA-DR, -DQ, class I), anti-interleukin-2 receptor (IL-2R) and anti-CD1. Sections from all hypertrophic scars showed an anomalous expression of HLA-DR molecules on keratinocytes and fibroblasts. Moreover hypertrophic scars were characterized by dense infiltrates of IL-2R-positive cells and by the presence of abundant Langerhans (CD1+) cells in the epidermis and dermis. These results support the hypothesis that immunologic mechanisms play an important role in hypertrophic scarring and point to an involvement of cell-mediated immune phenomena.
Characterization of homologous restriction factor (HRF20) in human skin and leucocytes
Authors: SAYAMA K , SHIRAISHI S , SHIRAKATA Y , KOBAYASHI Y , OKADA N , OKADA H , MIKI Y 
Published: July 2010

SUMMARYHomologous restriction factor with a molecular weight of 20 kD (HRF20) is a membrane protein that inhibits assembly of the membrane attack complex of homologous complement. Distribution of HRF20 in normal human skin was studied. The plasma membrane of keratinocytes was stained, and the intensity of the staining pattern was higher in the basal cell layer than in the granular layer. Endothelial cells of blood vessels in the dermis were also stained. The molecular weight of HRF20 on erythrocytes and epidermis is 16 kD, determined by Western blot analysis. Those of polymorphonuclear cells and lymphocytes appeared as two bands, a major band of 20 kD and a minor band of 16 kD. Susceptibility of HRF20 to phosphatidylinositol-specific phospholipase C (PIPLC) was examined. After PIPLC treatment of the sections, HRF20 was not detected on the epidermis and was very slightly expressed on the blood vessels. These results indicate that HFR20 attaches to keratinocytes and blood vessels via phosphatidylinositol, regulating the formation of membrane attack complexes of homologous complement on the cell membrane.
Cellular immunity in experimental Echinococcus multilocularis infection. I. Sequential and comparative study of specific in vivo delayed-type hypersensitivity against E. multilocularis antigens in resistant and sensitive mice
Authors: LIANCE M , BRESSON-HADNI S , MEYER J P , HOUIN R , VUITTON D A 
Published: July 2010

SUMMARY
Species- or strain-related differences in receptivity of intermediate hosts to E. multilocularis larvae could be related to differences in specific cellular immune response of the host. In order to test this hypothesis, we assessed the delayed-type hypersensitivity (DTH) to E. multilocularis antigens (EmAg) in mice of three strains differing by their sensitivity (AKR and C57BL.6) or resistance (C57BL.10) to E, multilocularis infection. DTH was determined by measuring in vivo the foot-pad response 24 h after an EmAg antigenic challenge. The level of positive response was evaluated in immunized mice; however, a typical DTH response was only observed by immunizing mice with a strong adjuvant schedule. Course of DTH in the immunized mice was shown to be somewhat different in sensitive and resistant mice. The differences were much more marked in mice infected with proliferative E. multilocularis larvae. The levels of the footpad response was significantly higher in resistant mice, although the peak of the reaction was obtained later than in sensitive mice. DTH. expressed by the foot-pad response against EmAg, remained significant for the entire period of observation in sensitive as well as in resistant mice. There was no correlation between receptivity of the murine hosts and levels of specific antibodies against EmAg. These results suggest a relationship between resistance to E. multilocularis infection and intensity and/or course of DTH in mice. The resistance could be mediated by some particularities of the in situ cellular immune response in the periparasitic granuloma.
Long-term cultures of human peripheral blood lymphocytes with recombinant human interleukin-2 generate a population of virtually pure CD3+CD16-CD56- large granular lymphocyte LAK cells
Authors: ROUSSEL E , GERRARD J M , GREENBERG A H 
Published: July 2010

SUMMARYIt has been reported that lymphocytes from peripheral blood (PBL) cultured with interleukin-2 (IL-2) produce predominantly CD16+ lymphokine-activated killer (LAK) cells. We developed a two-step method to generate LAK cells from human PBL in long-term cultures (10–12 days) with recombinant human IL-2 (rhIL-2) and characterized the evolving LAK cell population by testing its phenotype and cytotoxic activity as a function of time. The starting PBL displayed some natural killer (NK) cytotoxicity but no LAK activity. At day 6, the cells were a mixed population of about 80% CD3+ and 6% CD16+ cells. Little proliferation was evident but strong LAK activity was detected. After 10–12 days, major cell expansion had occurred and they were essentially a pure (&gt;90%) CD3+CD16-CD56- cell population large granular lymphocyte (LGL) by morphology that displayed strong non-MHC-restricted killing activity (&gt; 200 lytic units). Over the same period of time, the CD16+ cells had almost completely regressed in these cultures. This preferential induction of CD+ LAK cells was not an effect of IL-2 concentration as 10 U/ml was as effective as 500 U/ml. Further characterization revealed a major population of CD4+ (60%) and CD8+ (30%) with a smaller fraction (&lt;9%) of γδ+ cells. These results indicate that a virtually pure CD3+ LAK cells population was produced with long-term cultures of lymphocytes from peripheral blood in rhIL-2, in which active proliferation of the CD3+ but not CD16+ cells occurred.
Inhibition by FK506 of established lesions of collagen-induced arthritis in rats
Authors: ARITA C , HOTOKEBUCHI T , MIYAHARA H , ARAI K , SUGIOKA Y , KAIBARA N 
Published: July 2010

SummaryWe investigated the superior poteney of the immunosuppressive agent FK506 on collagen-induced arthritis in rats. In our initial studies, we demonstrated that only one shot administration of FK506 at a dose of 10 mg/kg on the same day as type II collagen immunization suppressed the incidence of arthritis completely as well as humoral and delayed-type hypersensitivity (DTH) skin lest responses to type II collagen. Yet no major side effects were observed in the rats treated with such a high dose of FK506. Additional studies demonstrated that pretreatment with FK506 on day — 7 or day — 3 was effective in suppressing the severity of arthritis and immune responses to type II collagen. The immunosuppressive effect of a single high-dose administration of FK506 continued for at least 1 week in this animal model of arthritis. A single administration of FK506 at a dose of 10 mg/kg on day 12 or 15, after the clinical onset of arthritis, was also effective in suppressing the severity of arthritis and immune response to type II collagen. We conclude that FK506, in this model, possesses an important, curative action when applied therapeutically. The outlook of FK506 treatment in clinical autoimmunity is promising at present.
Modulation of lymphocyte proliferation by enzymes that degrade amino acids
Authors: CHUANG J C , YU C L , WANG S R 
Published: July 2010

Summary
In a previous study we demonstrated thirteen amino acids to be essential and two to be partially essential for lymphocyte proliferation. Arginine is one of the essential amino acids, and the highly purified arginase strongly inhibited lymphocyte proliferation. The modulation of lymphocyte growth by various amino acid-degrading enzymes was studied. Peripheral lymphocytes were cultured in RPMI 1640 with or without amino acid-degrading enzyme for 72h. A total of 17 commercial L-amino acid-degrading enzymes were studied. At 10 μg/ml, both lysine decarboxylase and asparaginase completely inhibited lymphocyte proliferation, arginase resulted in 78% inhibition and tyrosinase 57% inhibition. Other enzymes inhibited less than 20% lymphocyte proliferation; they included alanine dehydrogenase, arginine decarboxylase, aspartase, glutamic decarboxylase, glutamic dehydrogenase, glutaminase, histidase, histidine decarboxylase, leucine dehydrogenase, phenylala-nine decarboxylase, phenylalanine hydroxylase, tryptophanase, and tyrosine decarboxylase. All four enzymes that strongly inhibited lymphocyte proliferation degraded amino acids that are essential for lymphocyte growth.
Monoclonal process in primary Sjögren's syndrome and cross-reactive idiotype associated with rheumatoid factor
Authors: KATSIKIS P D , YOUINOU P Y , GALANOPOULOU V , PAPADOPOULOS N M , TZIOUFAS A G , MOUTSOPOULOS H M 
Published: July 2010

SummaryMonoclonal or oligoclonal B cell products have been described in the sera and urine of patients with primary Sjögren's syndrome (PSS). In addition, monoclonal expansion of plasma cells has been found in the exocrine glands of PSS patients with circulating monoclonal Bcell products. The goal of this study was to raise an anti-idiotypc to a cryoprecipitablc monoclonal IgM kappa rheumatoid factor (RF) from a PSS patient. Using the F(ab′)2 fragments of the rabbit IgG anti-idiotype, an idiotype-specific ELISA was developed and sera from 32 patients with PSS (13 with monoclonal IgMκ), 33 with rheumatoid arthritis, three with rheumatoid arthritis + Sjögren's syndrome (SS), 30 with systemic lupus erythematosus, six with Waldcnslröm's macroglobulinaemia, and 20 healthy controls were tested. The idiotype was primarily found in PSS patients with circulating monoclonal IgMκ and more often in those who had a ratio of κ:λ intracytoplasmically positive plasma cells greater than 3:1 in the lymphocytic infiltrates of minor salivary glands, and systemic manifestations. The idiotype was also found in PSS and rheumatoid arthritis patients without circulating monoclonal cryoglobulins as well as in two of the six patients with Waldenstrom's macroglobulinaemia. Our results suggest that the monoclonal process observed in PSS could involve restricted idiotypic clones that are susceptible to malignant transformation.
Temporary breakdown of immunological tolerance to dsDNA and nucleohistone antigens in rabbits infected with rinderpest virus
Authors: IMAOKA K , KANAI Y , YOSHIKAWA Y , YAMANOUCHI K 
Published: July 2010

Summary
The rabbit-passaged L strain of rinderpest virus (RV) causes the transient induction of anti-nuclear antibodies (ANA) in rabbits. It has been shown by an indirect immunofluorcscence test that the target antigens of these ANA arc DNA and/or DNA-histone complexes (nucleohistone). Here detailed examinations of the target antigens were carried out by ELISA, and it was revealed that rabbit sera contained three types of antibodies: antibodies reading equally with both dsDNA and ssDNA; those reacting with ssDNA alone: and those reacting with nucleohistone. Epitopes recognized by the third type consisted of complexes of dsDNA and H2A + H2B or of dsDNA and H2B. All types of antibodies were antigen specific. Since the diversity of ANA among experimental rabbits was large, it was suggested that genetic background is important in the induction of anti-dsDNA antibodies in this system. Moreover, early induction of antibodies to nucleohistone and the rapid disappearance of ANA suggest that B cell proliferation maturation for continuous production of AN A requires factors other than RV infection. This system may help elucidate the mechanisms of ANA induction and the development of autoimmune diseases.