Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis.
Human glioblastoma is a highly lethal tumor that is known for its immune inhibitory capabilities. B7-homologue 1 (B7-H1), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert costimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H1 in human glioma cells in vitro and in vivo. Although lacking B7.1/2 (CD80/86), all 12 glioma cell lines constitutively expressed B7-H1 mRNA and protein. Exposure to IFN-gamma strongly enhanced B7-H1 expression. Immunohistochemical analysis of malignant glioma specimens revealed strong B7-H1 expression in all 10 samples examined, whereas no B7-H1 expression could be detected on normal brain tissues. To elucidate the functional significance of glioma cell-related B7-H1 expression, we performed coculture experiments of glioma cells with alloreactive CD4+ and CD8+ T cells. Glioma-related B7-H1 was identified as a strong inhibitor of CD4+ as well as CD8+ T-cell activation as assessed by increased cytokine production (IFN-gamma, interleukin-2, and interleukin-10) and expression levels of the T-cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (mAb 5H1). B7-H1 expression may thus significantly influence the outcome of T-cell tumor cell interactions and represents a novel mechanism by which glioma cells evade immune recognition and destruction.
Wintterle
Sabine
S
Department of Neurology, Medical School, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany.
Schreiner
Bettina
B
Mitsdoerffer
Meike
M
Schneider
Dagmar
D
Chen
Lieping
L
Meyermann
Richard
R
Weller
Michael
M
Wiendl
Heinz
H
D015703:Antigens, CD; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D060890:B7-H1 Antigen; D001798:Blood Proteins; D045744:Cell Line, Tumor; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D005910:Glioma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D010455:Peptides; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins; D010455:Peptides; D012333:RNA, Messenger