title: Human astrocytes are only partially competent antigen presenting cells. Possible implications for lesion development in multiple sclerosis.
abstract: Highly purified astrocyte cultures from human embryonic brain were examined for their capacity to present antigen to human leukocyte antigen (HLA) class II compatible, cytolytic CD4+ T lymphocytes. Most astrocytes constitutively expressed HLA class I products and LFA-3 (CD58). Constitutive expression of HLA class II, LFA-1 alpha (CD11a) and ICAM-1 (CD54) was lower and varied among different cultures, while LFA-2 (CD2) was absent. IFN-gamma alone or in combination with TNF-alpha strongly enhanced expression of HLA class I, HLA-DR, -DP, -DQ, LFA-1 alpha and ICAM-1, but did not affect expression of LFA-2 (CD2) and LFA-3 (CD58). TNF-alpha alone induced only HLA class I and ICAM-1, but not HLA class II or LFA-1 alpha. Cytokine treated, but not untreated astrocytes were able to present protein (auto-)antigens to specific T lymphocyte lines. Astrocytes expressing appropriate major histocompatibility complex class II products were lysed by CD4+ T cells specific for myelin basic protein or tetanus toxoid. The lytic response was antigen dose dependent and HLA-DR restricted. It could be blocked by antibodies against HLA-DR determinants and against the adhesion molecules LFA-1 alpha and ICAM-1. In remarkable contrast to their susceptibility to T cell lysis, antigen presenting astrocytes were not only completely unable to induce T cell proliferation but even inhibited proliferation. The results indicate that, although human astrocytes have the potential to present protein antigens to CD4+ T cells, they do not induce the co-stimulatory factors required to trigger the complete T cell activation programme.
authors.affiliation: Department of Neuroimmunology, Max-Planck-Institute of Psychiatry, Martinsried, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Weber
authors.forename: E
authors.initials: E
authors.lastname: Meinl
authors.forename: F
authors.initials: F
authors.lastname: Aloisi
authors.forename: C
authors.initials: C
authors.lastname: Nevinny-Stickel
authors.forename: E
authors.initials: E
authors.lastname: Albert
authors.forename: H
authors.initials: H
authors.lastname: Wekerle
authors.forename: R
authors.initials: R
authors.lastname: Hohlfeld
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001253:Astrocytes / Q000276:immunology*; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology; D002455:Cell Division; D002460:Cell Line; D000939:Epitopes; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D006680:HLA Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma