Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Antigenic Modulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed1990

Study on the expression of HLA-DR antigens, Fc IgG receptors and C3 complement component on lung macrophages in the primary lung carcinoma.

Expression of HLA-DR antigens and Fc IgG receptors as well as C3 complement component, was studied on patients with the primary lung carcinoma and in the control group of nonsmokers and smokers. Macrophages were isolated by broncho-alveolar lavage using bronchofiberoscope. The study was carried out before the treatment, within its course and during remission. The percentage of macrophages with HLA-DR antigens and Fc IgG receptors and C3 complement was observed to diminish before the treatment, after chemo- and radiotherapy as compared to the control. In the course of alpha interferon-treatment and at remission, the expression of HLA-DR antigens on macrophages increased in relation to the remaining groups of patients (p less than or equal to 0.05). The expression of Fc IgG receptors and C3 complement revealed no statistically significant differences. As the findings show the expression of HLA-DR antigens is modulated by interferon and has a tendency to increase in the course of convalescence. On the other hand, the expression of RFc IgG and RC3 complement shows great stabilization in the primary lung carcinoma and undergoes no changes either in the course of treatment or remission.

Antigens, Differentiation↗
PubMed2003

Biosynthesis and assembly of Group 1 capsular polysaccharides in Escherichia coli and related extracellular polysaccharides in other bacteria.

Extracellular and capsular polysaccharides (EPSs and CPSs) are produced by a wide range of bacteria, including important pathogens of humans, livestock, and plants. These polymers are major surface antigens and serve a variety of roles in virulence, depending on the biology of the producing organism. In addition to their importance in disease, some EPSs also have industrial applications as gelling and emulsifying agents. An understanding of the processes involved in the synthesis and regulation of CPSs and EPSs therefore potentially contributes to an understanding of the disease state, surface expression of protective antigens, and modulation of polymer structure to give defined physical properties. Escherichia coli has provided important model systems for EPS and CPS biosynthesis. Here we describe current knowledge concerning assembly of the Group 1 CPSs of E. coli and the conservation of similar mechanisms in other bacteria.

Antigens, Bacterial↗
PubMed1985

A mammalian host-vector system that regulates expression and amplification of transfected genes by temperature induction.

SV40-transformed simian cells that permit temperature-dependent regulation of vector DNA replication were isolated and characterized. These cell lines (ts COS cells) produce high levels of thermolabile large T antigen under the transcriptional control of the Rous sarcoma virus long terminal repeat. The ts COS cell lines can complement SV40 A gene mutants and support replication of SV40-origin containing vectors at 33 degrees C but not at 40 degrees C. It should now be possible to regulate the copy number of transfected plasmid DNA's and also maintain selectable vector sequences either as integrated DNA or as autonomously replicating episomes by modulating T antigen activity in ts COS cells.

Animals↗
PubMed1995

Effect of Dalton's lymphoma on the antigen presentation of murine peritoneal macrophages.

The antigen presenting ability of the murine peritoneal macrophages in response to coincubation, in vitro, with Dalton's lymphoma (DL) cells was investigated. The antigen presenting ability of the macrophages was observed to increase on in vitro treatment with lipopolysaccharide (LPS) (10 micrograms/ml) and cisplatin (5 micrograms/ml). Coincubation of the macrophages with DL cells or DL-conditioned medium (DLCM) decreased the antigen presenting ability of the cisplatin or LPS treated macrophages. However, the DL-associated macrophages (DLAM) showed increased antigen presenting ability as compared with the normal peritoneal macrophages which was further increased on in vivo administration of the cisplatin (8 mg/kg body weight). The effect of the in vitro treatment of the macrophages with DLCM and/or LPS on the synthesis of DNA, RNA and proteins was also studied. The DLCM was found to inhibit the RNA as well as the protein synthesis of the LPS-treated macrophages. This study shows that DL differentially modulates the antigen presenting ability of the macrophages depending on the local conditions of cellular interactions involved in the in vitro or the in vivo systems.

Animals↗
PubMed1994

Kinetics of the pleiotropic effect of interleukin 4 on the surface properties of human B-lymphoma cells.

Striking antigenic changes were elicited by interleukin 4 (IL-4) in the Farage human B-cell lymphoma line. After 2 days of incubation with IL-4 the expression of CD23, CD54 (ICAM-1), CD58 (LFA-3) was increased while the levels of CD21, CD22, CD38 were diminished. Prolonged incubation of Farage cells with IL-4 for 6-8 days led to increased expression of CD11a (LFA-1) CD39, CD40, and to disappearance of CD21 and CD38. The modulation of antigenic properties of Farage cells was associated with enhancement of their homotypic adhesiveness and the formation of giant clumps of cells. The recovery of Farage cells which had been exposed to IL-4 for six days was not complete and eleven days after withdrawal of the cytokine, these cells still displayed a lower level of CD21 and of CD38 than control cells. Cycling and non-cycling cells did not appear to differ in their antigenic properties, indicating that modification of the antigenic profile did not result from cell selection or cell arrest. These results showed that the pleiotropic effect of IL-4 on various cell surface structures on malignant human B cells proceeds at different rates suggesting that distinct metabolic pathways may regulate their expression.

Antigens, Neoplasm↗
PubMed1994

The ex vivo function and expression of function-associated antigens of peripheral blood neutrophils and monocytes.

The availability of recombinant human granulocyte and granulocyte-macrophage colony-stimulating factors (rhG-CSF and rhGM-CSF) has prompted many studies of the analysis of antigen expression and function of monocytes and neutrophils from patients receiving these factors as therapeutic agents. Preparatory procedures for leukocytes are known to alter antigen expression and so function. We therefore investigated the use of a novel procedure in which live leukocytes are analyzed by flow cytometry without isolation from blood. The expression levels of CD11b, CD13, CD14, CD16, and CD18 antigens and L-selectin (TQ1 and Leu-8 epitopes) on neutrophils and monocytes from 15 normal individuals were determined and compared with a previously used method in which the leukocytes were fixed and the erythrocytes lysed before analysis. Significant differences for the apparent expression of CD11b, CD18, and L-selectin were observed between the two methods. The reasons for this were investigated. Since the new method allowed analysis of live cells, we also investigated whether modulation of antigen expression could be determined following receptor agonist interaction. This was found to be easily achievable, and we advocate using the new procedure where possible for the ex vivo analysis of function and function-associated antigens on monocytes and neutrophils.

Adult↗
PubMed2002

Effect of Trypanosoma cruzi released antigens binding to non-infected cells on anti-parasite antibody recognition and expression of extracellular matrix components.

It has been proposed that antigens released by Trypanosoma cruzi sensitize vertebrate cells leading to their destruction by the immune response raised against the parasite. Here, we characterized antigens released by trypomastigotes of T. cruzi that bind to non-infected cells and investigated biological consequences of this adsorption. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of antigens released by [(35)S]-methionine-labeled parasites revealed the presence of polypeptides mainly ranging from 85 to 170 kDa that were specifically recognized by sera from chronically T. cruzi infected rabbits. Polypeptides of 85-110 and 160-170 kDa bound to non-infected epithelial, fibroblast and muscle mammalian cell lines, which thus became targets for anti-T. cruzi antibody binding. Cysteine-proteinase, but not trans-sialidase, was detected among the cell-bound antigens, and purified cysteine-proteinase was adsorbed to non-infected cells. Immunoelectron microscopic studies showed that parasite antigens were mainly released as membrane vesicles that adhered to membrane microvilli and were internalized by mammalian cells. We provide evidence that adsorption of parasite antigens induced an increase in expression of extracellular matrix (ECM) components (fibronectin, laminin and type I collagen) by sensitized cells. Thus, our data reinforce the idea that in vivo T. cruzi released antigens might be involved in the establishment of inflammation, sensitizing non-infected host cells and triggering an immune response against parasite antigens. Further, our data showed that antigen sensitization modulates biological cell functions as ECM expression that could mediate cell-cell or parasite-host cell interactions, contributing to the establishment of inflammation.

Adsorption↗
PubMedDate not supplied

Immunophenotypical changes of T lymphocytes in the elderly.

BACKGROUND: Substantial changes in both representation and function of T lymphocyte subsets have been reported with advancing age. However, till now, no systematic studies focused on age-dependent changes in the expression intensity of the major T lymphocyte surface receptors. OBJECTIVE: The present study was undertaken in order to establish age-related differences in lymphocyte subpopulations by simultaneously measuring three surface antigens in young and elderly people. METHOD: Peripheral blood T cell subsets from 20 healthy elderly individuals and 15 healthy young adult donors were examined by means of a quantitative three-color flow cytometry method. RESULTS: Activated (HLA-DR+) and memory (CD45RO+) T cells, CD3+CD7- T lymphocytes, and cells expressing natural killer (NK) markers (CD3-CD56+ NK cells and CD3+CD56+ T lymphocytes) were expanded, whereas T lymphocytes expressing the adhesion molecule CD62L were lower in elderly compared with young donors. In addition to alterations in the percentages of T cell subsets during senescence, several changes in the intensity expression of T cell antigens were also detected. CD3 antigen expression was downregulated on total T lymphocytes as well as on the memory T cell subset, while CD56+ T cells exhibited increased CD3 levels. Moreover, CD2 expression, unchanged on NK cells, was upregulated on T lymphocytes from elderly subjects. CD3+CD7- T cells exhibited increased expression of CD8 antigen, while the intensity expression of HLA-DR on activated T cells and CD7 on both T and NK lymphocytes was decreased. T cells from elderly subjects also exhibited higher expression of CD50 and CD62L adhesion molecules as compared with young ones. CONCLUSION: These T cell antigen expression modulations during senescence, in addition to the alteration in the frequency of the various T lymphocyte subsets, could contribute to the complex remodeling of the immune function characteristic of the elderly.

Adult↗
PubMed1986

Sex-dependent effects of non-H-2 loci on lethal GVH reaction induced across an H-2 barrier.

We have studied the influence of DBA/2 non-H-2 antigens on the lethal graft-versus-host reaction (GVHR) developed across an H-2 barrier. (DBA/2 X B10.D2)F1 X B10.D2 (H-2d) backcross (BC) mice were typed for their allelic constitution at nine genetically independent chromosome markers and used as individual cell donors simultaneously for two to three (DBA/2 X B10.D2)F1 recipients incompatible for DBA/2 non-H-2 antigens alone and two to three (DBA/2 X B10.BR)F1 recipients incompatible for DBA/2 non-H-2 antigens and H-2k. The results showed that, when compared with that developed in a control group incompatible for H-2k alone [B10.D2----(B10.D2 X B10.BR)F1]; the GVHR mortality seen in the presence of an additional incompatibility for DBA/2 non-H-2 antigens [(DBA/2 X B10.BR)F1 recipients] is significantly delayed but only in female mice. An analysis of individual BC donors indicated that this protective effect of DBA/2 non-H-2 antigens correlates with incompatibility for gene(s) linked to the Pgm-1 chromosome marker. In contrast, incompatibility for gene(s) linked to Mod-1 and Es-3 markers accelerates GVHR mortality, but only in male mice. Finally, the results obtained with (DBA/2 X B10.D2)F1 and (DBA/2 X B10.BR)F1 recipients were compared; they showed that the intensity of the GVHR developed by cells from individual BC donors against a given set of DBA/2 non-H-2 antigens correlates well with that developed by the same BC donor against the same set of non-H-2 antigens plus H-2k. We conclude that certain non-H-2 genes (and antigens) can modulate the intensity of the GVHR developed across an H-2 barrier. The number of such genes is probably great; their effects are strong and complex, and can be sex-dependent.

Animals↗
PubMed2003

Differential effect of HIV-1 protease inhibitors on P-glycoprotein function in multidrug-resistant variants of the human CD4+ T lymphoblastoid CEM cell line.

BACKGROUND: P-glycoprotein causing multidrug resistance (MDR) and limiting the efficacy of antineoplastic drugs and protease inhibitors (PIs) is expressed in human CD4+ T lymphocytes, one of the main targets of HIV, in a range of pharmacological barriers and at varying degrees in non-Hodgkin's lymphoma and Kaposi's sarcoma. METHODS: The differential effect of PIs on P-glycoprotein function was studied by measuring drug efflux inhibition, MDR-reversing ability and MAb UIC2 epitope modulation in MDR variants of the human T lymphoblastoid CEM cell line. RESULTS: The treatment of MDR cells with PIs induces different UIC2 epitope modulations indicating a differential recognition and binding of these antiviral drugs by MDR1 P-glycoprotein. In fact, ritonavir, saquinavir and indinavir act differently to the P-glycoprotein blocker in CEM-VBL10 cells. The MDR level of these cells was markedly affected by ritonavir and saquinavir in the order, while the PI indinavir does not seem to compete with the P-glycoprotein drug transport function. In CEM-VBL100 cells, expressing a very high number of P-glycoprotein molecules, only ritonavir acts as an efficient drug efflux inhibitor and MDR-reversing agent. CONCLUSION: The HIV-1 PIs ritonavir and saquinavir even at different levels act as genuine P-glycoprotein substrates by inhibiting dye substrate efflux, modulating UIC2 epitope and reversing drug resistance. Conversely, at least in the in vitro system used in the present study, the PI indinavir does not significantly alter P-glycoprotein drug transport activities and function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Monoclonal antibody ST1 identifies an antigen that is abundant in the axolotl and newt limb stump but is absent from the undifferentiated regenerate.

Monoclonal antibodies (mAb) utilized in regeneration studies to date identify antigens that are up-regulated in the blastema. We obtained a monoclonal antibody, designated ST1 (Stump 1), that is reactive to an extracellular matrix (ECM) antigen exhibiting the opposite distribution; ST1 is an abundant antigen of the limb stump soft tissues but is absent from within the blastema. The border between abundance and absence of mAb ST1 reactivity was sharp and extended as a concavity into the stump. This distinct dichotomy led to further studies relevant to understanding how this extracellular matrix antigen is modulated during regeneration. mAb ST1 reactivity decreased in the internal tissues at the distal end of the limb prior to blastema formation and remained absent until the onset of differentiation. The initial decrease in mAb ST1 reactivity was dependent on the combined effects of injury and the wound epithelium but was nerve independent. At blastema stages of regeneration, the distribution of tenascin, ascertained by mAb MT1 reactivity, closely matched the area without reactivity to mAb ST1. The spatial and temporal distribution of the ST1 antigen in unamputated limbs and during regeneration did not correspond to any previously described ECM component.

Ambystoma mexicanum↗
PubMed1989

Internalization and shedding of Lym-1 monoclonal antibody following interaction with surface antigens of a cultured human B cell lymphoma.

Modulation of surface antigens of Raji Burkitt's lymphoma cells by monoclonal antibody Lym-1 was investigated by flow cytometry and radioimmunoassay (RIA). Raji cells, treated with antibody conjugated with FITC, became bright green as determined by FACS and the FITC-labeled Lym-1 remained associated with target cells for up to 48 hr after incubation at either 4 or 37 degrees C. Lym-1 antibody linked with biotin also bound to Raji cells and rendered these cells highly reactive with avidin-phycoerythrin (APE). However, the APE fluorescence intensity measured by FACS decreased substantially when Raji cells were cultured at 37 degrees C for 1 hr prior to APE exposure but not when incubation was carried out at 4 degrees C, indicating a disappearance of antibody from the surface of the metabolically active cells. This process was time dependent with a total loss of surface-bound biotinylated antibody occurring over a period of approximately 2 hr. Raji cells exposed to both fluoresceinated and biotinylated Lym-1 in a double labeling experiment became positive to both reagents. The flow cytometric profile was not altered when these cells were incubated for 1 hr at 4 degrees C followed by reaction with APE. However, they failed to react with APE when the 1-hr incubation took place at 37 degrees C despite the fact that they remained FITC positive, suggesting that the antibody with its fluorescent label had entered the cells. Utilizing 131I-labeled Lym-1 it was determined that approximately 50% of initially bound antibody had dissociated from the cells within the first 2 hr of incubation at 37 degrees C, although the remainder persisted with targets for up to 48 hr. The HPLC protein profile indicated that the radioactivity found in the culture supernatants and cytoplasm was associated with whole antibody, degradation products, and Ig complexes with antigen. Therefore, the present findings suggest that Lym-1 Ig molecules react with cell surface antigens and are rapidly internalized and shed, resulting in the disappearance of antibody from the surface membrane of Raji cells.

Antibodies, Monoclonal↗
PubMed2005

Phosphotidylinositol-3 kinase-mediated signals in mice immunized with the 57 kDa major antigenic outer-membrane protein of Shigella dysenteriae type 1.

Antigen-specific T-cell signalling via T-cell antigen receptor stimulation was carried out in BALB/c mice immunized with the 57 kDa major antigenic component of Shigella dysenteriae 1 outer-membrane proteins. In presence of anti-CD3, the 57 kDa antigen was found to increase the level of IL-2 significantly instead of IL-4. IL-2 production in T cells was consistent with an increase in intracellular free Ca(2+) [(Ca(2+))i] concentration. The antigen-specific modulation was observed during T-cell signalling, with enhanced release of [(Ca(2+))i]. IL-2-receptor stimulation via IL-2 did not significantly induce the release of IL-2 with consistent intracellular Ca(2+) production. Furthermore, the protein tyrosine kinase was activated during anti-CD3 stimulation, which up-regulated the phosphatidylinositol kinase of p85-mediated serine kinase protein kinase-C of p70. Phosphoinositide-specific kinases are regulated by the phosphorylation of tyrosine kinase through the activation of the T-cell antigen receptor. The above findings indicate that phosphotidylinositol-3 kinase-mediated signals are up-regulated through [(Ca(2+))i], which is essential for Th1-type responses.

Animals↗
PubMed2000

Modulation of HLA-G antigens expression by human cytomegalovirus: specific induction in activated macrophages harboring human cytomegalovirus infection.

After infection, human CMV (HCMV) establishes a latent and persistent infection in immature myeloid progenitors and peripheral blood monocytes. Completion of the HCMV life cycle is possible upon maturation of monocytes to tissue macrophages and under permissive circumstances, e.g., immunosuppression. We investigated the hypothesis that HLA-G molecules could be induced during HCMV reactivation in activated macrophages to favor virus dissemination. In this study, we provide evidence that HLA-G Ags are produced during viral reactivation in macrophages generated after allogeneic stimulation of HCMV latently infected monocytes. While HLA-G surface expression is up-regulated, classical MHC-I molecules are partially down-regulated by HCMV. In vivo, bronchoalveolar macrophages collected from patients suffering from acute HCMV pneumonitis also express HLA-G molecules. The direct correlation between HLA-G Ag induction and HCMV infection was confirmed in U-373 MG astrocytoma cells. Soluble HLA-G expression is stimulated upon HCMV infection, and this modulation depends on the cooperative action of the two immediate-early-1 pp72 and immediate-early-2 pp86 products. Because HLA-G transcription is active in macrophages and U-373 MG astrocytoma cells, it is likely that the modulation of HLA-G protein expression during HCMV replication occurs at a post-transcriptional level. Our data suggest that induction of HLA-G molecules could be an additional mechanism that helps HCMV to subvert host defenses.

Astrocytoma↗
PubMed1992

Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the alpha-chain of the human interleukin-2 receptor.

The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the alpha-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2R alpha chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.

Amino Acid Sequence↗
PubMed1992

Effects of immunomodulatory cytokines on the presentation of tumor-associated antigens by epidermal Langerhans cells.

The recognition and presentation of tumor-associated antigens by cutaneous antigen-presenting cells (APC) may play an important role in the establishment of effective defense mechanisms against newly emerging tumors in the skin. Recent data demonstrate the ability of I-A+ epidermal cells (Langerhans cells) to present tumor-associated antigens for the induction of protective tumor immunity and elicitation of delayed-type hypersensitivity against the murine spindle cell tumor, S1509a. Furthermore, the local cytokine microenvironment in the vicinity of a cutaneous neoplasm may regulate the ability of resident epidermal APC to initiate and/or to elicit protective immunity against incipient cutaneous neoplasms. This article summarizes the effects of granulocyte-macrophage/colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), transforming growth factor-beta (TGF beta), and interferon-gamma (IFN gamma) on the modulation of antigen presentation by epidermal APC. Our data indicate that these cytokines significantly and differentially modify the ability of epidermal cells to present tumor-associated antigens and that their effects differ with regard to induction of primary immunity (sensitization) or elicitation of secondary immune responses.

Adjuvants, Immunologic↗
PubMed1998

Gallium arsenide modulates proteolytic cathepsin activities and antigen processing by macrophages.

Gallium arsenide (GaAs) is a semiconductor utilized in the electronics industry. Chemical exposure of animals causes a local inflammatory reaction, but systemic immunosuppression. Mice were administered i.p. 200 mg/kg GaAs crystals or latex beads, or vehicle. Five days after exposure, splenic macrophages were defective, whereas thioglycolate-elicited peritoneal macrophages (PEC) were more efficient in processing the Ag, pigeon cytochrome c, than vehicle control macrophages. Various aspects of the MHC class II Ag-processing pathway were examined. Both macrophage populations normally presented a peptide fragment to the CD4+ T cells. Surface MHC class II expression on the PEC was up-regulated, but splenic cells had normal MHC class II expression. PEC had elevated levels of glutathione and cysteine, major physiologic reducing thiols. However, the cysteine content of splenic macrophages was diminished. Proteolytic activities of aspartyl cathepsin D, and thiol cathepsins B and L were decreased significantly in splenic macrophages. On the other hand, thiol cathepsin activities were increased selectively in PEC. Latex bead-exposed PEC were not more potent APC, and their thiol cathepsin activities were unchanged, indicating that phagocytosis and nonspecific irritation were not responsible. The phenotype of PEC directly exposed to GaAs mirrored cytokine-activated macrophages, in contrast to splenic macrophages from a distant site. Therefore, GaAs exposure differentially modulated cathepsin activities in splenic macrophages and PEC, which correlated with their Ag-processing efficiency. Perhaps such distinct alterations may contribute to the local inflammation and systemic immunotoxicity caused by chemical exposure.

Adjuvants, Immunologic↗
PubMed2004

The therapeutic effects of PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation.

Poly(ADP-ribose) polymerase (PARP) activity has been implicated in the pathogenesis of several central nervous system (CNS) disorders. For example, the presence of extensive poly(ADP)ribosylation in CNS tissues from animals with experimental allergic encephalomyelitis (EAE) indicates that PARP activity may be involved in this inflammatory disease process. Using PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl], a selective PARP inhibitor, we studied the mechanisms through which PARP activity may contribute to the onset of acute EAE. PLSJL mice immunized with myelin antigens were treated with PJ34, and the effects on the progression of EAE and several other parameters relevant to the disease process were assessed. PJ34 exerted therapeutic effects at the onset of EAE that were associated with reduced CNS inflammation and the maintenance of neurovascular integrity. Expression of genes encoding the intercellular adhesion molecule-1 (ICAM-1) and the inflammatory mediators interferon-gamma, tumor necrosis factor-alpha, and inducible nitric-oxide synthase were decreased in CNS tissues from drug-treated animals. Administration of PJ34 biased the class of myelin basic protein (MBP)-specific antibodies elicited from IgG2a to IgG1 and IgG2b and modulated antigen-specific T-cell reactivity. Therefore, the mode of action of PJ34 at the onset of EAE is likely mediated by a shift in the MBP-specific immune response from a proinflammatory Th1 toward an anti-inflammatory Th2 phenotype.

Adjuvants, Immunologic↗