Adult human glial cells can present target antigens to HLA-restricted cytotoxic T-cells.
T-lymphocyte recognition of antigen either on antigen-presenting cells (APC) necessary for the generation of an immune response or on target cells during the effector phase of a cellular immune response requires expression of HLA molecules. Although immune mechanisms operate in many disease processes of the central nervous system (CNS), cells of the CNS generally express low levels of HLA molecules. In this study, the potential for upregulation of HLA molecules on adult human glial cells was examined. Moreover, the functional implication of this upregulation was assessed by the capacity of glial cells to process and present target antigens to HLA class I-restricted influenza-specific and class II-restricted myelin basic protein (MBP)-specific CTL lines. Glial cells cultured from adult human surgical brain specimens or cells from established glioblastoma multiforme cell lines were studied. Lysis by antigen-specific CTLs was dependent on treatment of the target cell with interferon-gamma. The lysis was HLA restricted and antigen specific. The results indicate that adult human glial cells can process and present antigen to HLA-restricted CTLs but require the upregulation of HLA molecules. These findings have implications for infectious and autoimmune diseases of the CNS.
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
S
S
Dhib-Jalbut
C V
CV
Kufta
M
M
Flerlage
N
N
Shimojo
H F
HF
McFarland
D000938:Antigen-Presenting Cells / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology; D001927:Brain Diseases / Q000209:etiology; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005909:Glioblastoma / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000276:immunology; D009457:Neuroglia / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation
D005904:Glial Fibrillary Acidic Protein; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D007371:Interferon-gamma