Cyclosporine inhibits macrophage-mediated antigen presentation. 1986

D A Palay, and C W Cluff, and P A Wentworth, and H K Ziegler

The influence of cyclosporine on antigen-specific, macrophage-dependent T cell activation was analyzed in vitro. Murine T cell activation by antigens derived from Listeria monocytogenes was monitored by the production of interleukin 2. Pretreatment (2 hr, 37 degrees C) of macrophages with cyclosporine resulted in a cell population with a markedly diminished capacity to support the activation of T lymphocytes. When cyclosporine-pretreated macrophages were added to cultures of untreated T cells and antigen, the dose of cyclosporine that produced 50% inhibition (ID50) was 1.5 micrograms/ml, and if antigen was present during the drug pretreatment, the ID50 was 0.6 micrograms/ml. Pretreatment of T cells also inhibited their subsequent activation by antigen and untreated macrophages, but a higher dose of cyclosporine was required to produce similar inhibition (ID50 = 4.4 micrograms/ml). Additional experiments focused on the mechanism of inhibition of antigen presentation when macrophages were pretreated with the drug. The addition of interleukin 1 or indomethacin to the cultures did not alter the inhibitory effect of cyclosporine. Under conditions that produced greater than 90% inhibition of antigen presentation, macrophage surface Ia expression was not altered, and the uptake and catabolism of radiolabeled antigen remained normal. Thus, cyclosporine had profound effects on antigen presentation that appear to be unrelated to decreases in interleukin 1 production, increases in prostaglandin production, decreases in Ia expression, or changes in antigen uptake and catabolism.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008809 Mice, Inbred C3H An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research. Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D003524 Cyclosporins A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection. Cyclosporines
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000938 Antigen-Presenting Cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors. Accessory Cells, Immunologic,Antigen-Presenting Cell,Immunologic Accessory Cells,Accessory Cell, Immunologic,Cell, Immunologic Accessory,Cells, Immunologic Accessory,Immunologic Accessory Cell,Antigen Presenting Cell,Antigen Presenting Cells,Cell, Antigen-Presenting,Cells, Antigen-Presenting
D000949 Histocompatibility Antigens Class II Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen. Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte

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