Monitoring the antitumor response of naive and memory CD8 T cells in RAG1-/- mice by positron-emission tomography.
Therapeutic antitumor immunity depends on a highly migratory CTL population capable of activation and trafficking between lymphoid and tumor-bearing microanatomic sites. We recently adapted positron-emission tomography gene expression imaging for noninvasive, longitudinal localization and quantitation of antitumor T lymphocyte migration in vivo. In this study, we apply this system to enumerate the temporal accumulation of naive vs memory T cells. Naive or memory OT-1 CD8(+) T cells, retrovirally marked with the sr39TK gene, were adoptively transferred into RAG1(-/-) animals bearing EL-4 or EG.7 (an OVA-expressing subline), and repetitively imaged by microPET over several weeks. Memory cells demonstrated early accumulation and apparent proliferation, with large T cell numbers at the Ag-positive tumor as early as day 1 after T cell transfer. Naive T cells did not accumulate in the E.G7 tumor until day 8, and reached only 25% of the peak levels achieved by memory T cells. Both naive and memory cells eradicated the Ag-expressing tumor at a comparable density of intratumoral T cells (2-4 x 10(6)/g). However, due to the slower rate of T cell expansion and continued tumor growth, naive cells required approximately 10-fold higher Ag-specific precursor frequency to reach a tumoricidal cell density. As recently reported, memory but not naive T cells accumulated in local lymph nodes and lungs, where they persisted as a resident population after tumor eradication. Positron-emission tomography-based immunologic imaging is a noninvasive modality providing unique and meaningful information on the dynamics of the antitumor CTL response.
Su
Helen
H
Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
Chang
Daisy S
DS
Gambhir
Sanjiv S
SS
Braun
Jonathan
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D049268:Positron-Emission Tomography; D013234:Stem Cells / Q000166:cytology
D018398:Homeodomain Proteins; C064658:RAG-1 protein