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Human astrocytes are only partially competent antigen presenting cells. Possible implications for lesion development in multiple sclerosis.
- Source :
-
Brain : a journal of neurology [Brain] 1994 Feb; Vol. 117 ( Pt 1), pp. 59-69. - Publication Year :
- 1994
-
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.
- Subjects :
- Antigens, CD immunology
Antigens, Differentiation, T-Lymphocyte immunology
CD2 Antigens
CD58 Antigens
Cell Adhesion Molecules immunology
Cell Division
Cell Line
Epitopes
Humans
Intercellular Adhesion Molecule-1
Interferon-gamma immunology
Lymphocyte Function-Associated Antigen-1 immunology
Membrane Glycoproteins immunology
Receptors, Immunologic immunology
T-Lymphocytes cytology
T-Lymphocytes immunology
Tumor Necrosis Factor-alpha immunology
Antigen-Presenting Cells immunology
Astrocytes immunology
HLA Antigens immunology
Multiple Sclerosis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8950
- Volume :
- 117 ( Pt 1)
- Database :
- MEDLINE
- Journal :
- Brain : a journal of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 7511974
- Full Text :
- https://doi.org/10.1093/brain/117.1.59