15 results
Search Results
2. Diminished mitogen-induced T cell proliferation by Trypanosoma cruzi antigens associated with antigen-presenting cell modulation and CD3 signaling.
- Author
-
Gómez-Olarte S, Bolaños NI, Cuéllar A, Puerta CJ, and González JM
- Subjects
- Adult, Cell Proliferation physiology, Female, Humans, Lymphocyte Activation immunology, Male, Signal Transduction immunology, Trypanosoma cruzi, Antigen-Presenting Cells immunology, Antigens, Protozoan immunology, CD3 Complex immunology, Chagas Disease immunology, T-Lymphocytes immunology
- Abstract
Chronic infection by Trypanosoma cruzi decreases T cell proliferation and it is most likely accompanied by changes in signals required for activation. We assessed the effect of T. cruzi antigens on mitogen-induced proliferation of T cells from uninfected individuals and the association with the expression of molecules involved in antigen presentation, T cell costimulation and activation, and cytokine production. T. cruzi antigen exposure reduced mitogen-induced proliferation of CD4+ and CD8+ T cells in PBMC cultures, but only reduced mitogen-induced proliferation in the CD4+ T cells from sorted cell cultures cocultured with antigen-pulsed CD3- cells. CD40/CD80 and CD86 expression were reduced in antigen-pulsed DCs and monocytes, respectively. TNF-α, IL-10 and CCL17 levels were increased in cultures with antigen-pulsed CD3- cells, while CD3ζ chain expression was reduced in T cells from cultures with antigen. Our findings suggest that T. cruzi could alter T cell proliferation indirectly by downregulating costimulatory molecules and inducing the secretion of IL-10 and directly by decreasing TCR signaling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
3. Immunomodulatory effects of the HIV-1 gp120 protein on antigen presenting cells: implications for AIDS pathogenesis.
- Author
-
Conti L, Fantuzzi L, Del Cornò M, Belardelli F, and Gessani S
- Subjects
- Acquired Immunodeficiency Syndrome immunology, Antigen-Presenting Cells immunology, HIV Envelope Protein gp120 immunology, HIV-1 immunology, Humans, Macrophages immunology, Protein Binding, Signal Transduction, Acquired Immunodeficiency Syndrome etiology, Antigen-Presenting Cells metabolism, HIV Envelope Protein gp120 metabolism, HIV-1 metabolism
- Abstract
Antigen presenting cell (APC) function is central to the development of an effective anti-viral immune response. Among APC, monocytes, macrophages and dendritic cells (DC) form the principal non-T cell compartment involved in in vivo HIV infection, and these cells play important and well-established roles in multiple aspects of viral pathogenesis. HIV infection may result in APC defects, which could ultimately contribute to the loss of CD4+ T cell responses observed early in HIV infection, when the CD4+ T cell number is still within the normal range. Extensive in vitro studies have demonstrated that the envelope glycoproteins of HIV-1 exert profound influences on various cell populations of the immune system, including hematopoietic progenitors, T and B lymphocytes, monocytes/ macrophages and DC, as well as on neuronal cells. The demonstration of the presence of envelope proteins both free in the circulation and bound to the surface of CD4+ cells suggests that gp120 interactions with non-infected cells can influence cellular functions in vivo, thus contributing to the immunopathogenesis of AIDS. This paper provides an overview of the present knowledge on gp120 binding, signal transduction triggering and interference with macrophage and DC functions and it highlights the importance of this interaction in the pathogenesis of AIDS.
- Published
- 2004
- Full Text
- View/download PDF
4. 'Troy-bodies': antibodies as vector proteins for T cell epitopes.
- Author
-
Lunde E, Rasmussen IB, Eidem JK, Gregers TF, Western KH, Bogen B, and Sandlie I
- Subjects
- Animals, Antibodies genetics, Antibody Specificity, Histocompatibility Antigens Class II immunology, Humans, Immunoglobulin D immunology, Immunoglobulin Variable Region chemistry, In Vitro Techniques, Mice, Mice, Inbred BALB C, Models, Structural, Mutagenesis, Insertional, Nitrohydroxyiodophenylacetate, Protein Folding, Protein Structure, Tertiary, Recombinant Proteins immunology, Antibodies immunology, Antigen-Presenting Cells immunology, Epitopes immunology, Protein Engineering, T-Lymphocytes immunology
- Abstract
A major objective in vaccine development is the design of reagents that give a strong, specific T cell response. Targeting of antigens to antigen presenting cells (APC) results in enhanced antigen presentation and T cell activation. In this paper, we describe a novel targeting reagent denoted 'Troy-bodies', namely recombinant antibodies with APC-specificity and with T cell epitopes integrated in their C regions. We have made such antibodies with V regions specific for either IgD or MHC class II, and five different T cell epitopes have been tested. All epitopes could be introduced into loops of C domains without disrupting immunoglobulin (Ig) folding. Four have been tested in T cell activation studies, and all could be released and presented by APC. Furthermore, whether IgD- or MHC-specific, the molecules tested enhanced T cell stimulation compared to non-specific control antibodies in vitro as well as in vivo. Using this technology, specific reagents can be designed that target selected antigenic peptides to an APC of choice. Troy-bodies may therefore be useful for manipulation of immune responses, and in particular for vaccination purposes.
- Published
- 2001
- Full Text
- View/download PDF
5. Macrophage presentation of endogenous self-protein: the MHC class II presentation pathway is not accessible to intracellular C5 or alpha 1-antitrypsin.
- Author
-
Grant CF, Ali R, Povey S, and Stockinger B
- Subjects
- Animals, B-Lymphocytes immunology, Complement C5 biosynthesis, Dendritic Cells immunology, Humans, Macrophage Activation, Mice, Mice, Inbred A, Mice, Inbred CBA, Spleen immunology, T-Lymphocytes immunology, Antigen-Presenting Cells immunology, Autoantigens immunology, Complement C5 immunology, Histocompatibility Antigens Class II immunology, Macrophages, Peritoneal immunology, alpha 1-Antitrypsin immunology
- Abstract
This paper addresses the question of whether macrophages can present biosynthesized protein in a class II-restricted manner using the endogenous rather than the exogenous pathway of presentation. Two distinct self-antigens, the fifth component of complement (C5) and alpha 1-antitrypsin, were studied. Both antigens are serum proteins synthesized by hepatocytes and macrophages. To direct synthesis exclusively to macrophages chimeras were constructed by transfer of bone marrow from donors expressing the self-antigen into irradiated hosts deficient for the respective self-antigen. Macrophages from such mice were unable to present biosynthesized C5 to class II-restricted T cells, even when preactivated in vivo. While C5 production by macrophages is low and may not reach critical levels of intracellular protein required to access the class II presentation pathway, human alpha 1-antitrypsin, expressed as a transgene in mice, was synthesized at 600-fold higher levels than C5. Nevertheless, macrophage-synthesized alpha 1-antitrypsin in bone marrow chimeras was not presented in the context of class II--even in a mutant form which is sequestered in high amounts in the endoplasmic reticulum. We conclude that macrophages are unable to use the endogenous class II presentation pathway for these two model self-antigens. As a consequence MHC class II-restricted T cells specific for C5 and alpha 1-antitrypsin remain ignorant of the presence of self-antigen within macrophages and are neither tolerized nor rendered autoimmune.
- Published
- 1996
- Full Text
- View/download PDF
6. Modulation of immunity by ultraviolet radiation: key effects on antigen presentation.
- Author
-
Ullrich SE
- Subjects
- Animals, Cytokines physiology, Epidermis metabolism, Humans, Immunity physiology, Immunosuppression Therapy, Mice, Neoplasms, Experimental immunology, Photoreceptor Cells physiology, Skin cytology, Skin innervation, Skin radiation effects, Antigen-Presenting Cells radiation effects, Immunity radiation effects, Ultraviolet Rays
- Abstract
In addition to being the major cause of non-melanoma skin cancer, the ultraviolet radiation (UVR) present in sunlight is a potent immunosuppressive agent. Indeed, studies with mice and humans have indicated that the immune suppression induced by UVR is a risk factor for skin cancer development. These observations gave rise to the discipline of photoimmunology, which studies the interaction of electromagnetic radiation, primarily UVB (280-320 nm) light, with the immune system. The focus of this paper will be to review recent studies designed to unravel the mechanisms through which UVR suppresses immune reactivity. Particular emphasis is placed on the effects of UVR on antigen presentation.
- Published
- 1995
- Full Text
- View/download PDF
7. Antigen presentation of mycobacterial peptides to human T cell clones can be immunomodulated by adding an MHC-specific inhibitor.
- Author
-
Méndez-Samperio P
- Subjects
- Binding Sites, Antibody, Binding, Competitive, Clone Cells immunology, Humans, Lymphocyte Activation immunology, Peptide Fragments immunology, Tuberculosis immunology, Antigen-Presenting Cells immunology, Antigens, Bacterial immunology, HLA-DR1 Antigen immunology, Mycobacterium tuberculosis immunology, T-Lymphocytes immunology
- Abstract
The immunomodulation of T cell recognition by mycobacterial antigens was investigated using T cell clones activated with peptide-pulsed EBV-B cells. An HLA-DR1-restricted T cell clone from a patient with tuberculosis responded to peptide 65-85 from the 65-kDa protein of Mycobacterium tuberculosis in a dose-dependent manner, while no significant response was induced by antigen-nonpulsed EBV-B cells or EBV-B cells pulsed with an unrelated antigen (streptokinase/streptodornase). The observed binding to HLA-DR1 could be inhibited when the EBV-B cells were cultured in the presence of an excess of an HLA-DR1-restricted T cell epitope (residues 1-20) from the 19-kDa protein of M. tuberculosis. This inhibition was dose-dependent. In other experiments, proliferation of a DR1-restricted T cell clone from a healthy individual which responded to peptide 1-20 was inhibited by an excess of peptide 65-85, confirming that these peptides are able to compete for the same DR1-binding site. Nevertheless, the T cell clone from the healthy individual showed a relatively lower percentage of inhibition compared with the T cell clone from a patient with tuberculosis. Furthermore, the intensity of this inhibition was reversed as the concentration of stimulatory peptide was increased. The experiments described in this paper demonstrate the immunomodulation of mycobacterial antigen presentation by peptide competition at the level of MHC-binding sites. These data may be important for an understanding of the interactions involved in the mycobacterial cell-mediated immune recognition.
- Published
- 1993
- Full Text
- View/download PDF
8. A new method for measuring clustering in suspension between accessory cells and T lymphocytes.
- Author
-
Gant VA, Shakoor Z, and Hamblin AS
- Subjects
- Carbocyanines, Cell Aggregation, Flow Cytometry, Humans, Immunologic Memory, In Vitro Techniques, Lymphocyte Activation, Microscopy, Fluorescence, Antigen-Presenting Cells cytology, T-Lymphocytes cytology
- Abstract
Specifying the molecular basis and clinical significance of cluster formation between antigen-presenting cells and T lymphocytes will be important in many areas of immunology. In this paper we describe a novel and reproducible technique for measuring cluster formation in suspension between purified human blood monocytes and purified autologous T lymphocytes, and its application to determining the effects of recall antigens and mitogen. Blood monocytes and T lymphocytes from eight normal subjects were separately prelabelled with two different carbocyanine dyes prior to co-culture in suspension with or without antigen (PPD, SKSD) or mitogen (PHA). At 24 h the co-cultures were examined for cluster formation by ultraviolet microscopy and flow cytometry. Control experiments showed that the carbocyanine dyes were non-toxic in vitro, that cell labelling was stable for culture periods up to 120 h, and that the two dyes did not leak from cell to cell. By this technique we measured the proportion of monocytes clustering one or more T lymphocytes in the presence and absence of recall antigen or PHA. There was a close correlation between visual and flow cytometric measurement of monocyte: T lymphocyte clustering (p < 0.001) as well as a close relationship between the ability of the two recall antigens to increase the extent of clustering above baseline (p < 0.001). Antigen-increased cluster formation did not correlate with baseline clustering, unlike PHA-increased clustering, which was related to baseline levels (p = 0.02), suggesting the operation of distinct mechanisms. The method is applicable to measuring cell-cell associations in suspension during extended periods of culture, as well as for the study of agents which might modify intercellular adhesion processes.
- Published
- 1992
- Full Text
- View/download PDF
9. Expression of I-region-associated antigen (Ia) and interleukin 1 by subcultured human endothelial cells.
- Author
-
Wagner CR, Vetto RM, and Burger DR
- Subjects
- Cells, Cultured, Endothelium immunology, Humans, Immunity, Cellular, Macrophages immunology, T-Lymphocytes immunology, Antigen-Presenting Cells immunology, Histocompatibility Antigens Class II immunology, Interleukin-1 biosynthesis, Veins immunology
- Abstract
Activation of T cells requires three signals from an antigen-presenting cell: antigen, Ia determinants (HLA-D region determinants in man), and interleukin 1 (IL-1). Recent evidence has suggested that macrophages, dendritic cells, epidermal Langerhan's cells, and endothelial cells can each function as antigen-presenting cells (APC). If these cell types can independently function as APC, they should synthesize Ia determinants and secrete IL-1. To determine if endothelial cells fulfill these requirements, we have propagated human umbilical vein endothelial cells by serial subculture for extended periods of time and assessed Ia expression and IL-1 secretion. The endothelial cells were subcultured for 8 months (approximately 20 subcultures) and were found to display classic morphology and immunofluorescent staining for the endothelial cell-specific marker Factor VIII-related antigen. In a separate paper we have shown that these subcultured endothelial cells can present antigen to T cells in a HLA-D region-restricted fashion (C. R. Wagner, R. M. Vetto, and D. R. Burger, Subcultured human endothelial cells can independently function as fully competent antigen-presenting cells, accepted for publication, Hum. Immunol.). In this paper we present evidence demonstrating that extensively subcultured endothelial cells biosynthesize both HLA-DR and HLA-DS molecules after exposure to T cells and antigen or to a supernatant from antigen-activated T cells. Evidence is also presented that when endothelial cells are cultured in the presence of lipopolysaccharide they secrete a molecule(s) with IL-1 activity as assayed by LBRM-33-IA5 cell line production of interleukin 2.
- Published
- 1985
- Full Text
- View/download PDF
10. The role of Langerhans cells in antigen presentation.
- Author
-
Katz SI, Cooper KD, Iijima M, and Tsuchida T
- Subjects
- Antibodies, Monoclonal immunology, Humans, Interleukin-1 biosynthesis, Interleukin-1 radiation effects, Langerhans Cells radiation effects, T-Lymphocytes immunology, Antigen-Presenting Cells immunology, Histocompatibility Antigens Class II immunology, Langerhans Cells immunology
- Abstract
Epidermal Langerhans cells are dendritic bone marrow-derived cells which synthesize and express Ia antigens. During the past decade, in vitro studies have demonstrated that they play a critical role in the induction of many types of T-cell responses. Specifically, Langerhans cells are effective antigen-presenting cells in allogeneic and antigen specific proliferative and cytotoxic T-cell responses. This paper reviews these functions and suggests areas of future investigations into the mechanisms involved in T-cell activation by Langerhans cells.
- Published
- 1985
- Full Text
- View/download PDF
11. Role of self carriers in the immune response and tolerance. XII. Effect of epitope density and antigen-presenting cell phenotype on the presentation of hapten-modified self for the induction of immunity or tolerance in vitro.
- Author
-
Cogswell JP and Scott DW
- Subjects
- Animals, Antigens, Surface physiology, Cell Line, Dendritic Cells immunology, Dose-Response Relationship, Immunologic, Epitopes, Haptens, Histocompatibility Antigens Class II immunology, In Vitro Techniques, Interleukin-1 physiology, Mice, Neoplasms, Experimental immunology, T-Lymphocytes immunology, T-Lymphocytes, Regulatory immunology, Antibody Formation, Antigen-Presenting Cells physiology, Autoantigens immunology, Immune Tolerance
- Abstract
The data presented in the accompanying paper (J. P. Cogswell, R. P. Phipps, and D. W. Scott, Cell. Immunol. 114, 55-70, 1988) indicate that certain macrophage-like and lymphoid dendritic-like (P388AD.2) tumor lines which express major histocompatibility encoded class II (Ia) antigens and produce interleukin 1 (IL-1) are uniquely able to present hapten-modified self (HMS) in an immunogenic fashion in vivo. In the current study, the relationship between phenotype and function has been confirmed utilizing a completely in vitro system. This investigation revealed that B-cell priming required T cells restricted to P388AD.2's I-A antigens. In addition, exogenous IL-1 reconstituted the response of an IL-1-deficient tumor (P388AD.2-ILd), although it had no effect on the other nonimmunogenic Ia+ tumor lines. Unlike the in vivo system, effective B-cell tolerance was induced when P388AD.2 was modified with high concentrations (10 mM) of hapten or when highly haptenated tumor was added to 0.1 mM TNBS-modified P388AD.2. These results suggest that positive regulation of in vitro immune responses to HMS is dependent upon the phenotype of the accessory cell carrier (with lymphoid dendritic-like cells being unusually potent), while negative regulation is associated with high epitope density. This system now allows the dissection of the properties of different accessory cells and the signals required for B-cell priming or tolerance induction.
- Published
- 1988
- Full Text
- View/download PDF
12. Modulation of Ia and photoreactive antigen on antigen-presenting cells: fun with a photoprobe.
- Author
-
Thomas DW, Eades L, Wilson C, and Solvay MJ
- Subjects
- Animals, Azides immunology, Cell Line, Cross-Linking Reagents, Epitopes, Fixatives, Hybridomas immunology, Lymphocyte Activation, Mice, Mice, Inbred Strains, Photochemistry, Rats, Tuberculin immunology, Antigen-Presenting Cells immunology, Histocompatibility Antigens Class II immunology, T-Lymphocytes immunology
- Abstract
To identify the antigen-specific recognition complex containing elements from T cells and antigen-presenting cells (APC), a photoactivatable antigen system was developed which could potentially crosslink the complex during the specific cellular responses. In this paper we describe the development of this system using murine T-cell hybridomas responding to stimulator cells chemically conjugated with N-hydroxysuccinimidyl 4-azidobenzoate (HSAB) and genetically restricted by I-Ad. In initial experiments it was found that several I-Ad-positive B-cell lines were nonstimulatory when coupled with HSAB, but that I-Ad-positive P388D1 macrophage-like cells were efficient stimulators of HSAB-specific T-cell responses. These results suggested that the relevant HSAB coupled surface structure was not likely I-Ad. To substantiate this point, Ia-positive or Ia-negative P388D1 cells were initially coupled with HSAB and the expression of Ia was modulated by the addition and withdrawal of Con A-stimulated spleen cell supernatant fluid through several days of culture. Under these conditions, efficient stimulation was only observed when Ia was expressed, although the HSAB antigen was continuously present. In other experiments it was found that exposure of HSAB-coupled APC to light selectively eliminated their stimulatory capacity for HSAB-specific T hybridomas, suggesting that the light-induced crosslinking by HSAB directly eliminates the antigenic determinant. This antigen system allows a unique opportunity to manipulate the antigen during specific cellular interactions, and to introduce covalent crosslinking of the specific antigen recognition complex that may allow its isolation and characterization.
- Published
- 1985
- Full Text
- View/download PDF
13. The demonstration of cell surface antigens on T cells, B cells and accessory cells in paraffin-embedded human tissues.
- Author
-
Collings LA, Poulter LW, and Janossy G
- Subjects
- Antibodies, Monoclonal, Cell Membrane immunology, HLA-DR Antigens, Histocompatibility Antigens Class II analysis, Histological Techniques, Humans, Leprosy immunology, Lymphocytes cytology, Palatine Tonsil immunology, Paraffin, Skin immunology, Antigen-Presenting Cells immunology, Antigens, Surface analysis, B-Lymphocytes immunology, T-Lymphocytes immunology
- Abstract
This paper describes a method for processing fresh tissue that allows immunohistological analysis on paraffin sections. The method is based on the use of periodate-lysine-paraformaldehyde fixation. The effects of variation in fixation time, concentration of paraformaldehyde, dehydration, clearing, wax embedding and enzyme treatment of cut sections were examined. An optimal processing procedure was established that retains good tissue morphology and allowed 21 out of 27 monoclonal antibodies tested to be used successfully on paraffin sections to identify all major cell subpopulations by their membrane antigenic characteristics. The value of this approach in studying the immunopathology of potentially dangerous infectious diseases and in leukaemia/lymphoma diagnosis is discussed.
- Published
- 1984
- Full Text
- View/download PDF
14. Human airway epithelial cells present antigen to influenza virus-specific CD8+ CTL inefficiently after incubation with viral protein together with ISCOMATRIX
- Author
-
Martina M. Geelhoed-Mieras, Albert D. M. E. Osterhaus, Ron A. M. Fouchier, Guus F. Rimmelzwaan, Adrianus C. M. Boon, J.T.M. Voeten, and Virology
- Subjects
Antigen presentation ,Orthomyxoviridae ,Genetic Vectors ,Antigen-Presenting Cells ,Respiratory Mucosa ,Biology ,CD8-Positive T-Lymphocytes ,Epitope ,Cell Line ,Interleukin 21 ,Interferon-gamma ,Viral Proteins ,Antigen ,Adjuvants, Immunologic ,Cytotoxic T cell ,Humans ,Antigen-presenting cell ,Immunity, Mucosal ,General Veterinary ,General Immunology and Microbiology ,HLA-A Antigens ,Public Health, Environmental and Occupational Health ,Gene Transfer Techniques ,Epithelial Cells ,biology.organism_classification ,Flow Cytometry ,Virology ,Chromium Radioisotopes ,CTL ,Infectious Diseases ,Retroviridae ,Molecular Medicine ,T-Lymphocytes, Cytotoxic - Abstract
In the present paper, an in vitro model was established in which the interaction between influenza virus-specific CD8+ T cells and human airway epithelial cells can be studied. To this end, the human lung epithelial cell line A549 was transduced with the HLA-A*0201 gene. This MHC class I allele is involved in the presentation of the immunodominant M1 58–66 cytotoxic T lymphocyte (CTL) epitope of the influenza A virus matrix protein. The A549-HLA-A2 cells and a CD8+ T cell clone specific for the M1 58–66 epitope were used to evaluate ISCOMATRIX ® (IMX), which is considered a potential mucosal adjuvant for influenza vaccines, for its capacity to activate virus-specific CTL after incubation with epithelial cells. It was found that virus infected epithelial cells activated virus-specific CTL efficiently. However, incubation of epithelial cells with ISCOMATRIX ® and recombinant M1 protein activated CD8+ T cells inefficiently, unlike the incubation of C1R cells expressing a HLA-A2 trans gene or HLA-A2+ B-lymphoblastoid cells with these reagents. It was concluded that this lack of antigen presentation by epithelial cells indicate that these cells are not subject to killing by virus-specific CTL upon instillation with ISCOMATRIX ® -based vaccines, which may be a favorable property of mucosal vaccines.
- Published
- 2004
15. What is an immunological synapse?
- Author
-
Cristina Delgado-Martin, José Luis Rodríguez-Fernández, and Lorena Riol-Blanco
- Subjects
Immunological Synapses ,T cell ,T-Lymphocytes ,Immunology ,Antigen presentation ,Antigen-Presenting Cells ,Cell Communication ,Biology ,Cell–cell contact ,Microbiology ,Immunological synapse ,Synapse ,Antigen presenting cells ,medicine ,Animals ,Humans ,Antigen-presenting cell ,Cytoskeleton ,Dendritic cell ,Dendritic Cells ,Cell biology ,Cytoskeletal proteins ,Cytoskeletal Proteins ,Infectious Diseases ,medicine.anatomical_structure ,Lymphocyte ,Signal Transduction - Abstract
[EN] Review paper [ES] Artículo de Revisión, Immunological synapses (IS) are emerging as highly organized 3D structures -formed by surface and cytoplasmic signalling and cytoskeletal molecules - that assemble at the zone of contact between a T cell and an antigen presenting cell (APC). The IS control functions that allow APC and T cells modulate the immune response., This work was supported by the Ministerio de Educación y Ciencia (grants BFI-2001-0228 and SAF2005-00801) and Red de Investigación en Inflamación y en Enfermedades Reumáticas (RIER) (grant RD08/0075 (RETICS Program/Instituto de Salud Carlos III)) (J.L.R.-F.), a scholarship associated with grant PI021058, conferred by the Fondo de Investigación Sanitaria (L.R.-B.), and fellowship Formación de Personal Investigador (FPI) conferred by the Ministerio de Educación y Ciencia (C.D.-M.).
- Published
- 2010
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.