Human astrocytes are only partially competent antigen presenting cells : possible implications for lesion development in multiple sclerosis

• Published in: Brain (London, England : 1878) England : 1878), 1994-02, Vol.117 (1), p.59-69
• Main Authors: WEBER, F, MEINL, E, ALOISI, F, NEVINNY-STICKEL, C, ALBERT, E, WEKERLE, H, HOHLFELD, R
• Format: Article
• Language: English
• Subjects: Antigen-Presenting Cells - immunology; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Astrocytes - immunology; Biological and medical sciences; CD2 Antigens; CD58 Antigens; Cell Adhesion Molecules - immunology; Cell Division; Cell Line; Epitopes; HLA Antigens - immunology; Humans; Intercellular Adhesion Molecule-1; Interferon-gamma - immunology; Lymphocyte Function-Associated Antigen-1 - immunology; Medical sciences; Membrane Glycoproteins - immunology; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Receptors, Immunologic - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/117.1.59

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.