OX40 and Bcl-xL promote the persistence of CD8 T cells to recall tumor-associated antigen.
The molecular signals that allow primed CD8 T cells to persist and be effective are particularly important during cancer growth. With response to tumor-expressed Ag following adoptive T cell transfer, we show that CD8 effector cells deficient in OX40, a TNFR family member, could not mediate short-term tumor suppression. OX40 was required at two critical stages. The first was during CD8 priming in vitro, in which APC-transmitted OX40 signals endowed the ability to survive when adoptively transferred in vivo before tumor Ag encounter. The second was during the in vivo recall response of primed CD8 T cells, the stage in which OX40 contributed to the further survival and accumulation of T cells at the tumor site. The lack of OX40 costimulation was associated with reduced levels of Bcl-x(L), and retroviral expression of Bcl-x(L) in tumor-reactive CD8 T cells conferred greatly enhanced tumor protection following adoptive transfer. These data demonstrate that OX40 and Bcl-x(L) can control survival of primed CD8 T cells and provide new insights into both regulation of CD8 immunity and control of tumors.
Song
Aihua
A
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Tang
Xiaohong
X
Harms
Kate Marie
KM
Croft
Michael
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000502:physiology*; D051020:bcl-X Protein / Q000235:genetics / Q000502:physiology*
D000951:Antigens, Neoplasm; C494812:Bcl2l1 protein, mouse; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C476587:Taa1 protein, mouse; C505717:Tnfrsf4 protein, mouse; D051020:bcl-X Protein