In vitro priming of tumor-reactive cytolytic T lymphocytes by combining IL-10 with B7-CD28 costimulation.
Naive spleen cells from syngeneic mice generated tumor-reactive CTL following three cycles of in vitro culturing with IL-10 and cells from the P815 mouse mastocytoma that expressed the B7-1 or B7-2 costimulator. Unpurified as well as CD8-enriched naive splenocytes could be used for priming. The in vitro primed CTL were CD8+, and their recognition was MHC class I restricted. Both IL-10 and B7-transfected P815 cells were required for the priming. However, a combination of exogenous IL-10 and IL-2 in the presence of B7-negative wild-type P815 cells also induced tumor-reactive CTL. Injection of the neutralizing anti-IL-10 mAb JES-2A5 into mice reduced their ability to mount a primary CTL response after immunization with B7-1+ P815 cells, and inclusion of this mAb in the in vitro cultures inhibited a secondary CTL response. Adoptive transfer of the in vitro primed CTL had a therapeutic effect in mice with P815 established as an ascites tumor. Our results underscore an important role of IL-10 in the induction of a tumor-specific CTL response.
Yang
G
G
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
Hellström
K E
KE
Mizuno
M T
MT
Chen
L
L
D000818:Animals; D001201:Ascites / Q000276:immunology / Q000628:therapy; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes; D005260:Female; D016219:Immunotherapy, Adoptive; D016753:Interleukin-10 / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D012515:Mast-Cell Sarcoma / Q000628:therapy; D051379:Mice; D008811:Mice, Inbred DBA; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D000939:Epitopes; D016753:Interleukin-10