Rapid induction of OX40 ligand on primary T cells activated under DNA-damaging conditions.
We have previously demonstrated that normal human T cells either long-term repeatedly stimulated or freshly activated in vitro in the presence of TGF-beta express the cell surface T-cell costimulating molecule OX40 ligand (OX40L). To further elucidate the kinetics of OX40L expression by human T cells, we have examined whether cell proliferation was required for the expression of OX40L. Thus, normal fresh peripheral blood mononuclear cells were stimulated with immobilized anti-CD3 antibody in the presence of the DNA synthesis-blocking agents such as mitomycin C, 5-fluorouracil, or X-ray irradiation. Flow cytometric analyses demonstrated that a significant frequency of these DNA-damaged activated primary CD4+ and CD8+ T cells became OX40L+ as early as 1 hour after treatment. The OX40L induction on the DNA-damaged activated T cells was inhibited by treatment with either RNA or protein synthesis inhibitors, actinomycin D, or cycloheximide, respectively. Induced OX40L on T cells was functional because it bound recombinant OX40. These data indicate that human primary T cells are programmed to rapidly express functional OX40L molecules after stimulation under DNA-damaging conditions, demonstrating that the induction of OX40L by T cells is independent of cell proliferation. The clinical implications of these new findings are discussed.
Kondo
Kayo
K
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Okuma
Kazu
K
Tanaka
Reiko
R
Matsuzaki
Goro
G
Ansari
Aftab A
AA
Tanaka
Yuetsu
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D053282:CD27 Ligand / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D053285:CD30 Ligand / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D004249:DNA Damage; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016685:Mitomycin / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D053278:OX40 Ligand / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; D017252:CD3 Complex; D053285:CD30 Ligand; D019384:Nucleic Acid Synthesis Inhibitors; D053278:OX40 Ligand; D011500:Protein Synthesis Inhibitors; C505774:TNFSF8 protein, human; D016685:Mitomycin