Modulation of the H-2 antigenicity on the surface of murine peritoneal cells.
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Animals↗
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Results for “Antigenic Modulation”
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Modulated expression of human leucocyte antigen class I and class II determinants in hyperplastic and malignant human prostatic epithelium.
OBJECTIVES: To determine whether human prostatic carcinoma cells express Class I and/or Class II major histocompatibility complex (MHC) determinants and whether they might thus be immune-competent targets for cell-mediated cytotoxicity. MATERIALS AND METHODS: Immunohistochemistry, performed both before and after neuraminidase digestion, was employed to compare 13 benign prostatic hyperplasias with 42 primary and 44 metastatic prostatic carcinomas obtained from the United Kingdom and from the United States of America. Expression of beta 2-microglobulin was used as the marker of Class I and HLA-DR as the marker of Class II expression. RESULTS: Before desialylation, Class I MHC determinants were expressed in all of the benign hyperplasias, in 26% of primary carcinomas and in 14% of lymph node metastases. Cells expressing Class II determinants were identified in 69% of benign hyperplasias and in 2% of primary carcinomas, but in none of the lymph node metastases. After desialylation. Class I determinants were expressed in 100% of benign hyperplasias. 59% of primary carcinomas and 34% of the lymph node metastases. Class II determinants were expressed in 100% of benign hyperplasias, but only 19% of primary carcinomas and 5% of the lymph node metastases. While more than 50% of epithelial cells in each of the benign hyperplasias expressed MHCs, < 5% of the tumour cell populations in the positive malignant tissues (primary and metastatic) expressed MHCs, even after neuraminidase digestion. No correlation was found between expression of Class I or Class II MHC and Gleason morphological grade. CONCLUSIONS: Failure to express Class I and/or Class II MHC determinants is a common feature of the majority of human prostatic carcinoma cells. Absence of these recognition molecules may be associated with avoidance of immune-surveillance and contribute to the metastatic dissemination of this malignancy.
Epithelium↗
Modulation of immune responses following antigen administration by mucosal route.
Most microbial infections are either restricted to the mucosal membranes or the etiologic agents needed to transit the mucosa. Thus, it is desirable to stimulate a mucosal response following vaccination, to block both infection and disease development. Attenuated vaccine carriers mimic natural infections, triggering also mucosal responses. Similar results can be achieved by administering antigens with appropriate adjuvants. However, the delivery of antigens per se is not sufficient to engender a protective response. A successful immunization requires the elicitation of an appropriate type of immune response (e.g. antibodies vs. cell-mediated immunity, Th1 vs. Th2 helper pattern). Therefore, a successful vaccination strategy demands the choice of adequate antigens, and their appropriate delivery and/or formulation to promote the required quality of immune response. Different strategies to optimize the immune responses elicited following vaccine administration by the mucosal route are discussed.
Adjuvants, Immunologic↗
Modulation of HLA-DR antigens in the gingival epithelium in vitro by heat-killed Fusobacterium nucleatum and E. coli lipopolysaccharide.
The in vitro influence of the periodontopathic organism Fusobacterium nucleatum (FN) on gingival tissue was examined using an organ culture system. Treatment of gingival explants obtained from periodontally diseased sites with suspensions of FN, stimulated the expression of HLA-DR antigens by Langerhans cells (LC) in a dose-dependent fashion, and produced a maintenance of the LC markers T6 and ATPase. Similar effects were seen when E. coli lipopolysaccharide (LPS) was substituted for suspensions of FN. With both FN and LPS the expression of HLA-DR by gingival keratinocytes was maintained throughout the 72-h culture period, despite the cytotoxic effects of these agents. Using a variety of immunohistological techniques and a monoclonal antibody specific for the strain of FN used, it was possible to demonstrate the uptake of FN antigens by LC within the gingival epithelium.
Cell Count↗
Modulation of Langerhans cell surface antigen expression by recombinant cytokines.
This study examined the influence of cytokines on surface antigen expression by gingival Langerhans cells (LC) in organ culture, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) upregulated the expression of CD1a, HLA-DR and HLA-DP antigens on LC. TNF-alpha, interleukin-4 (IL-4), and transforming growth factor beta (TGF-beta) suppressed CD29 expression, while other cytokines, including interleukin-3 and granulocyte-macrophage colony stimulating factor, were without effect. No cytokines induced CD3, CD4, CD23, CD25 or CD45 RA antigen expression in organ culture. Since TNF-alpha and IL-6 can be secreted by keratinocytes, these molecules, together with interleukin-1, are likely to play a role in the local control of LC number and function within the epithelial milleu. Thus, alterations in cytokine secretion by keratinocytes may at least in part be responsible for variations in LC number and antigen expression which occur in oral mucosal disorders.
Antigens, CD↗
Expression of the Yersinia enterocolitica pYV-encoded type III secretion system is modulated by lipopolysaccharide O-antigen status.
We show that the expression of a Yersinia enterocolitica O:8 pYV-encoded type III secretion system was altered in a rough mutant (YeO8-R) due to elevated levels of FlhDC. H-NS might underlie flhDC upregulation in YeO8-R, and the data suggest a relationship between the absence of O antigen and the expression of H-NS.
Bacterial Proteins↗
Role of M protein in pharyngeal colonization by group A streptococci in rats.
As the initial step in infection, group A streptococci (GAS) colonize either the nasopharyngeal mucosa or the skin of humans. A number of virulence factors have been implicated in the colonization phase of pathogenesis based upon their in vitro activities, but the in vivo data supporting their role in colonization of the host tissues is lacking. In this investigation, the potential requirement for M protein in pharyngeal colonization by GAS was explored by using near-isogenic strains in experimental animals studies. Fischer rats were infected by intranasal and oral inoculation with both M-positive and M-negative Streptococcus pyogenes strains. Colonization of the pharyngeal area by the streptococci was monitored at various time intervals. Both M-positive and M-negative strains colonized during the first week following infection, indicating that M protein was not necessary for this initial colonization. Two M-positive strains of S. pyogenes were recovered from the rats up to 23 weeks following inoculation, while the colonization levels for M-negative strains decreased rapidly in the second and third weeks, becoming negligible by the fourth week. This indicates a potential role for M protein in the persistence of colonization at this mucosal surface. Colonization of rats with either M-positive strain of S. pyogenes also resulted in the appearance of salivary and serum antibody responses. This in vivo model should allow further investigation into factors required for GAS disease, including the examination of the potential role of the host immune response both in modulation of the pharyngeal surface and in modulation of antigenic changes in M protein or other surface factors.
Adhesins, Bacterial↗
Downregulation of mitogen-activated protein kinases by the Bordetella bronchiseptica Type III secretion system leads to attenuated nonclassical macrophage activation.
Bordetella bronchiseptica utilizes a type III secretion system (TTSS) to establish a persistent infection of the murine respiratory tract. Previous studies have shown that the Bordetella TTSS mediated cytotoxicity in different cell types, inhibition of NF-kappaB in epithelial cells, and differentiation of dendritic cells into a semimature state. Here we demonstrate modulation of mitogen-activated protein kinase (MAPK) signaling pathways and altered cytokine production in macrophages and dendritic cells by the Bordetella TTSS. In macrophages, the MAPKs ERK and p38 were downregulated. This resulted in attenuated production of interleukin- (IL-)6 and IL-10. In contrast, the Th-1-polarizing cytokine IL-12 was produced at very low levels and remained unmodulated by the Bordetella TTSS. In dendritic cells, ERK was transiently activated, but this failed to alter cytokine profiles. These results suggest that the Bordetella TTSS modulates antigen-presenting cells in a cell type-specific manner and the secretion of high levels of IL-6 and IL-10 by macrophages might be important for pathogen clearance.
Adenylate Cyclase Toxin↗
Modulation of transporter associated with antigen processing (TAP)-mediated peptide import into the endoplasmic reticulum by flavivirus infection.
In contrast to many other viruses that escape the cellular immune response by downregulating major histocompatibility complex (MHC) class I molecules, flavivirus infection can upregulate their cell surface expression. Previously we have presented evidence that during flavivirus infection, peptide supply to the endoplasmic reticulum is increased (A. Müllbacher and M. Lobigs, Immunity 3:207-214, 1995). Here we show that during the early phase of infection with different flaviviruses, the transport activity of the peptide transporter associated with antigen processing (TAP) is augmented by up to 50%. TAP expression is unaltered during infection, and viral but not host macromolecular synthesis is required for enhanced peptide transport. This study is the first demonstration of transient enhancement of TAP-dependent peptide import into the lumen of the endoplasmic reticulum as a consequence of a viral infection. We suggest that the increased supply of peptides for assembly with MHC class I molecules in flavivirus-infected cells accounts for the upregulation of MHC class I cell surface expression with the biological consequence of viral evasion of natural killer cell recognition.
ATP-Binding Cassette Transporters↗
How does airway inflammation modulate asthmatic airway constriction? An antigen challenge study.
During the late-phase (LP) response to inhaled allergen, mediators from neutrophils and eosinophils are released within the airways, resembling what occurs during an asthma attack. We compared the distribution of obstruction and degree of reversibility that follows a deep inspiration (DI) during early-phase (EP) and LP responses in nine asthmatic subjects challenged with allergen. Heterogeneity of constriction was assayed by determining frequency dependence of dynamic lung resistance and elastance, airway caliber by tracking airway resistance during a DI, and airway inflammation by measuring inflammatory cells in induced sputum postchallenge. Despite a paucity of eosinophils in the sputum at baseline (<1% of nonsquamous cells), asthmatic subjects showed a substantial EP response with highly heterogeneous constriction and reduced capacity to maximally dilate airways. The LP was associated with substantial airway inflammation in all subjects. However, five subjects showed only mild LP constriction, whereas four showed more marked LP constriction characterized by heterogeneous constriction similar to EP. Bronchoconstriction during LP was fully alleviated by administration of a bronchodilator. These findings, together with the impaired bronchodilatory response during a DI, indicate a physiological abnormality in asthma at the smooth muscle level and indicate that airway inflammation in asthma is associated with a highly nonuniform pattern of constriction. These data support the hypothesis that variability in responsiveness among asthmatic subjects derives from intrinsic differences in smooth muscle response to inflammation.
Adult↗
The antimicrobial/elastase inhibitor elafin regulates lung dendritic cells and adaptive immunity.
Infections with bacteria and viruses such as adenovirus are a feature of chronic lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be instrumental in the generation of disease exacerbations. We have previously shown in acute models that elafin (a lung natural chemotactic molecule for macrophages and neutrophils, with potent antimicrobial and neutrophil elastase inhibitor activity) is upregulated in infection and modulates innate immunity. Here we present data using two independent systems of elafin overexpression in vivo (recombinant adenovirus [Ad-elafin] and an elafin transgenic mouse line) to examine the function of elafin in adaptive immunity. We show that elafin increases the number (immunofluorescence) and activation status (flow cytometric measurement) of CD11c+/MHCII+ lung dendritic cells in vivo. Analysis of cytokines produced by spleen and lung cells, and of antibodies measured in serum and bronchoalveolar lavage fluid, shows that the immunity induced is biased toward a type 1 response (production of IL-12, IFN-gamma, and IgG2a). Furthermore, elafin overexpression protected mice against further challenge with Ad-LacZ, as assessed by antibody levels and neutralization titer, as well as LacZ expression in lung tissue. Thus, the pleiotropic molecule elafin has significant potential in modulating antigen-presenting cell numbers and activity, and could be beneficial in mucosal protective strategies.
Adenoviridae↗
In vivo modulation of proliferating cell nuclear antigen in growth plate chondrocytes from normal, hypophysectomized, growth hormone-treated hypophysectomized rats: a comparative immunohistochemical study with image analysis.
Growth hormone (GH) regulates the proliferation and maturation of chondrocytes in the epiphyseal growth plate, in which a temporal dimension is superimposed on the septal organization of the tissue. In this study we investigated the in vivo effects of hypophysectomy (Hypox) and injection of GH into Hypox animals (Hypox + GH) on the proliferative activity of the growth plate chondrocytes. We assessed the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in paraffin-embedded tissues, using monoclonal antibody PC 10 against PCNA combined with immunogold-silver staining. We subjected the immunostained sections to computer-based image analysis by ACAS 570 interactive laser cytometry employing a conventional microscopic light source. Hypox was carried out on 20 rats at 8 weeks of age, half of which received a hypodermic injection of human GH at a dose of 1 IU/kg twice a day for 1 week after the operation. Another group of five rats of the same age were used as normal controls. In normal rats, a distinct PCNA immunoreaction was observed in the proliferative zone, whereas a remarkable diminution of the number of immunoreactive cells in this zone was apparent in Hypox animals. On the other hand, marked hyperplasia of PCNA-positive cells was seen in the proliferative zone of the Hypox + GH rat growth plate. The immunoreactive cells of this zone in Hypox + GH animals exhibited increased nuclear size and staining intensity of PCNA compared with those in normal and Hypox rats. These findings were further confirmed by computer-based image analysis of the specimens in terms of cell integrated value, area, perimeter, and shape factor. These different patterns of PCNA expression may imply that GH specifically promotes the proliferation phase of the chondrocytes in the proliferative zone. The data also suggest that GH influences not only cell replication activity but also cell kinetics of chondrocytes in the growth plate during their lifespan.
Animals↗
Fine-tuning of immune responses by SLAM-related receptors.
The modulation of antigen receptor signals is important for a productive immune response. The main function of the recently identified members of the signaling lymphocyte activating molecule (SLAM)-related receptors (SRR) is the fine-tuning of immune cell activation. Disruption of SRR function is the cause for severe immune disorders such as X-linked lymphoproliferative syndrome (XLP), where XLP patients carry a mutation in SLAM-associated protein (SAP) (SH2D1A), an important adaptor molecule for the signal transduction of SRR. Recent data also suggest that SRR may play a role in autoimmune diseases and the function of hematopoietic stem and progenitor cells. Here, we review the current understanding of SRR function in different immune cells.
Animals↗
Modulation of MHC class II antigen expression in human myoblasts after treatment with IFN-gamma.
Some investigators have proposed myoblast transfer as a potential therapy for the treatment of Duchenne muscular dystrophy. Little is known about the immunobiology of myoblast transplantation. Transplantation rejection is mediated to a large extent by CD8+ T cells, which recognize alloantigens encoded by class I HLA genes, and by CD4+ T cells, which recognize alloantigens encoded by class II HLA genes. Gamma interferon (IFN-gamma) is a potent inducer of HLA class II molecules as well as beta 2-microglobulin, which is co-expressed with HLA class I. IFN-gamma may be a critical cytokine involved in graft rejection. We purified human myoblasts by flow cytometry and incubated them in vitro for varying time periods with recombinant human IFN-gamma. The inducibility of HLA-DR and -DP molecules raises a note of caution concerning possible rejection phenomenon which might occur following myoblast transplantation.
Cells, Cultured↗
Early life events in allergic sensitisation.
The timing of events leading to allergic sensitisation has become a very important area in the attempt to halt the dramatic increase in the prevalence of diseases such as asthma, eczema and hay fever. Recent research has demonstrated that events taking place during the gestational period may well play a role in determining whether or not a genetic susceptibility becomes translated into disease processes. Maternal atopy seems to have an important effect on the developing immune response of the infant and increases the chances of the child developing allergy in later life. Maternal IgE, IgG and amniotic fluid cytokines, combined with the presence of allergen in the feto-maternal environment are all possible factors involved in the ultimate outcome in terms of infant Th-1/Th-2 responses to common environmental antigens. Immune modulation at this stage of development may, in the future, be a way forward in the prevention of allergy.
Allergens↗
Large cell lymphoma transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma. A flow cytometric analysis of seven cases.
We studied 7 cases of large cell transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) immunophenotyped by multiparameter flow cytometry. The 6 women and 1 man ranged in age from 45 to 91 years. All had previous or concurrent evidence of CLL/SLL. Morphologic features and sites of involvement of the diffuse large B-cell lymphoma (DLBCL) were heterogeneous; 2 cases had paraimmunoblastic morphologic features. Six DLBCLs had an immunophenotype consistent with CLL: CD19+, CD5+, CD23+, and FMC7 negative (3 cases) or very dim (2 cases); 1 case was not studied for FMC7. CD20 was dim in 3 of these, moderate to bright in 2, and variable in 1. Surface immunoglobulin was dim in 2 cases and moderate or bright in 4. Five of 6 expressed CD38. Comparison with the immunophenotypes of the previous or coexistent CLL/SLL (4 of 6 cases) revealed minor modulations in antigen expression but no major alterations. The seventh DLBCL lacked CD5 expression, but otherwise had immunophenotypic features similar to CLL. These findings indicate that DLBCL arising in CLL/SLL tends to retain a CLL immunophenotype, in contrast with de novo CD5+ large cell lymphomas that uncommonly express such a phenotype.
ADP-ribosyl Cyclase↗
Effects of pranlukast on chemical mediators in induced sputum on provocation tests in atopic and aspirin-intolerant asthmatic patients.
BACKGROUND: Leukotrienes (LTs) are important in asthma, and LT modifiers modulate antigen-induced asthma. Overproduction of LT by suppression of cyclooxygenase activity is involved in patients with aspirin-intolerant asthma (AIA). METHODS: House dust mite (HDM) inhalation provocation tests were performed in HDM-sensitive asthmatic inpatients without AIA (HDM group; n = 6), and aspirin oral provocation tests were performed in AIA patients (ASA group; n = 7). Tests were repeated using the same regimen after 7 days of treatment with pranlukast, an LT receptor antagonist (LTRA). The effects of pranlukast on changes in sputum LTC(4)-LTD(4), eosinophil cationic protein (ECP), eosinophil count, urinary LTE(4)/creatinine, 11-dehydrothromboxane B(2) (11-dhTXB(2))/creatinine, serum LTC(4)-LTD(4), ECP, and peripheral blood eosinophil count, during immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) in the HDM group and during IAR in the ASA group for each test, were compared in each group. RESULTS: In the HDM group, IAR and LAR were observed. Sputum LTC(4)-LTD(4) and urinary LTE(4)/creatinine increased significantly both during IAR and LAR. Sputum ECP increased during IAR and further increased during LAR. Eosinophil count in the sputum did not increase during IAR but significantly increased during LAR. Pranlukast suppressed the fall in FEV(1) both during IAR and LAR (73.8% and 51.9%, respectively) and inhibited the increase in sputum eosinophil count during LAR and sputum ECP during IAR and LAR. In the ASA group, aspirin-induced IAR was associated with a fall in urinary 11-dhTXB(2)/creatinine, increased the levels of sputum LTC(4)-LTD(4) and ECP and urinary LTE(4)/creatinine. Pranlukast suppressed IAR and inhibited the increase of the level of sputum ECP, but failed to change aspirin-induced LT production in the sputum and urine. The levels of sputum LTC(4)-LTD(4) and urinary LTE(4)/creatinine in the stable phase in the ASA group were significantly greater than those in the HDM group. CONCLUSION: Our results indicated that HDM-provoked asthma is associated with overproduction of LT with an antigen-antibody reaction, while AIA is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade. LTRA may be useful against both types of asthma through inhibition of LT activity and eosinophilic inflammation of the airways.
Adult↗
Effect of macrophage colony-stimulating factor (M-CSF) on mouse immune responses in vivo.
We examined the effects of recombinant human M-CSF (rhM-CSF) on mouse macrophages and immune responses in vivo. Intraperitoneal administration of rhM-CSF (20-500 microgram/ml) increased Mac-1+ cell numbers in the peritoneal cavity. The tumoricidal activities of the macrophages from vehicle-administered (V-M phi) and from rhM-CSF-administered (M-M phi) mice were the same as those observed in vitro. However, when activated by lipopolysaccharide (LPS), the tumoricidal activity of M-M phi was stronger than that of V-M phi. Intravenous administration of rhM-CSF (500 micrograms/gk) increased the number of spleen cells. Flow cytometric analysis showed that administration of rhM-CSF increased Mac-1+, B220+ and NK 1.1+ cell counts in the spleen. However, CD4+ and CD8+ cell numbers did not change. Concomitant increases were observed in levels of IL-4 and IL-10 in mouse serum following rhM-CSF administration, but no significant changes were observed in the serum level of IFN-gamma. In experiments involving mouse immune responses, the administration of rhM-CSF reduced the contact sensitivity (CS) reaction against picryl chloride (PC) and augmented IgE production in response to 2,4-dinitrophenyl (DNP), but did not affect the production of either IgM or IgC1. These results suggest that administration of rhM-CSF not only activates murine macrophages, but modulates antigen-specific immune responses in vivo.
Animals↗