Immunosuppressive effects of transforming growth factor beta: inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response. 1991

S P Epstein, and R L Baer, and G J Thorbecke, and D V Belsito
Department of Dermatology, New York University School of Medicine, New York.

Recent reports show that transforming growth factor (TGF)-beta exerts a variety of immunosuppressive activities. The present study focuses on the effects of TGF-beta 1 on expression of Ia antigen by Langerhans cells. Although TGF-beta 1, in concentrations from 0.001 to 100 micrograms/ml, has no effect on constitutive expression of Ia antigen on these cells, the in vitro up-regulation of Ia antigen on the surface of LC by interleukin (IL)-1, tumor necrosis factor-alpha, interferon-gamma, IL-3, and granulocyte/macrophage-colony stimulating factor is inhibited by the concomitant addition of 1 microgram/ml TGF-beta 1. In contrast, TGF-beta 1 has no effect on the up-regulation induced by IL-2 or IL-6. In this report, the activity of TGF-beta closely resembles that of Cyclosporine A (CsA). Similar results are seen in vivo when either TGF-beta 1 (5 micrograms, intraperitoneally [ip], daily on days 0-3) or CsA (1 mg, subcutaneously [sc], twice daily on days 0-3) are given together with IL-2 (500 U, intraperitoneally [ip], twice daily on days 1-3) or interferon-gamma (4,000 U, ip, twice daily on days 1-3). Given the important role of Ia expression in cell-mediated immune reactions, the effect of TGF-beta on contact sensitivity was next investigated. In doses of 5 micrograms, ip, daily on days 6-8, TGF-beta inhibits the expression of contact reactivity in animals sensitized on day 0 and challenged on day 7. In contrast, no effect is observed on the induction of contact sensitivity in mice given TGF-beta 1 on days--1 to 2, sensitized on day 0, and challenged on day 7. The possible importance of antagonism between TGF-beta and other cytokines, especially IFN-gamma, involved in the elicitation of contact hypersensitivity reactions is discussed.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007801 Langerhans Cells Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS. Langerhans Cell,Dendritic Cells, Dermal,Dendritic Cells, Epidermal,Dendritic Cells, Skin,Dermal Dendritic Cells,Epidermal Dendritic Cells,Skin Dendritic Cells,Cell, Dermal Dendritic,Cell, Epidermal Dendritic,Cell, Langerhans,Cell, Skin Dendritic,Cells, Dermal Dendritic,Cells, Epidermal Dendritic,Cells, Langerhans,Cells, Skin Dendritic,Dendritic Cell, Dermal,Dendritic Cell, Epidermal,Dendritic Cell, Skin,Dermal Dendritic Cell,Epidermal Dendritic Cell,Skin Dendritic Cell
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010853 Picryl Chloride A hapten that generates suppressor cells capable of down-regulating the efferent phase of trinitrophenol-specific contact hypersensitivity. (Arthritis Rheum 1991 Feb;34(2):180). 2,4,6-Trinitro-1-chlorobenzene,1-Chloro-2,4,6-trinitrobenzene,Trinitrochlorobenzene,Chloride, Picryl
D003877 Dermatitis, Contact A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Contact Dermatitis,Dermatitis Venenata,Eczema, Contact,Hypersensitivity, Contact,Sensitivity, Contact,Contact Dermatitides,Contact Eczema,Contact Hypersensitivities,Contact Hypersensitivity,Contact Sensitivities,Contact Sensitivity,Dermatitides, Contact,Hypersensitivities, Contact,Sensitivities, Contact
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
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
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016212 Transforming Growth Factor beta A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk

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