期刊
JOURNAL OF IMMUNOLOGY
卷 176, 期 7, 页码 4459-4467出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.176.7.4459
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资金
- NCI NIH HHS [CA86306, CA16042, CA128697, CA09056] Funding Source: Medline
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 similar to 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.
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