4-1BB (CD137) controls the clonal expansion and survival of CD8 T cells in vivo but does not contribute to the development of cytotoxicity.
4-1BB is expressed on activated T cells. We analyzed the role of 4-1BB during the CD8 T cell response of OT-I TCR-transgenic T cells to ovalbumin. In vitro, blocking 4-1BB during peptide presentation reduced proliferation of naive CD8 T cells, but did not affect the generation of CTL. Using an in vivo adoptive transfer model, clonal expansion of CD8 T cells to whole protein in adjuvant was significantly reduced when 4-1BB was blocked, with 50-70% fewer CD8 T cells accumulating. This was due to a reduction in T cell division and to enhanced apoptosis of CD8 T cells that had undergone many divisions. T cells generated in the absence of 4-1BB were impaired in their ability to secrete IFN-gamma whereas CTL activity of the T cells that survived was unaffected. These findings demonstrate that 4-1BB contributes to clonal expansion, survival, and development of Tc1 cells when protein antigen is encountered by primary CD8 T cells in an inflammatory environment in vivo.
Cooper
David
D
Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Bansal-Pakala
Pratima
P
Croft
Michael
M
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002455:Cell Division; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D010047:Ovalbumin