Functional characterization of OX40 expressed on human CD8+ T cells.
In the present study, we investigated the expression of OX40 on human CD8(+) T cells with regard to expression induction, costimulatory function and possible involvement in cytotoxicity. Human CD8(+) T cells were purified from peripheral blood mononuclear cell (PBMC) of healthy donors and cocultured with allogeneic monocyte-derived dendritic cells. Flow cytometric analysis showed that expression of OX40 was induced on CD8(+) T cells within 1 day and increased to the maximum levels on day 3. An addition of anti-OX40 ligand (OX40L) mAb suppressed CD25 expression, proliferation and IFN-gamma production of CD8(+) T cells, suggesting that OX40 functions as a costimulatory molecule not only for CD4(+) T cells but also for CD8(+) T cells. In parallel, coculture of pre-activated CD8(+) T cells with OX40L-transfected murine epithelial cells (MMCE-OX40L) resulted in an increase in CD25 expression, proliferation and IFN-gamma producing cells, compared with that with the mock control (MMCE-mock). Finally, non-specific cytotoxic activity of preactivated CD8(+) T cells was examined using OKT3 hybridoma as target cells after coculture with these transfectants. Coculture with MMCE-OX40L induced slightly higher cytotoxicity of CD8(+) T cells than that with MMCE-mock. These results indicate that OX40 is induced transiently on CD8(+) T cells upon activation and its signals contribute to both clonal expansion and functional reinforcement.
Fujita
Tomoko
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyoku, Japan.
Ukyo
Naoya
N
Hori
Toshiyuki
T
Uchiyama
Takashi
T
D000911:Antibodies, Monoclonal / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D007371:Interferon-gamma