Monitoring the Antitumor Response of Naive and Memory Cd8 T Cells in Rag1-/- Mice by Positron-emission Tomography.
From: Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Apr 2006
- ISSN: 0022-1767
- Volume: 176
- Issue: 7
- Pages: 4459-67
- Medium: Print
- Language: English
- Citation (JAMA): Su Helen, Chang Daisy S, Gambhir Sanjiv S, et al. Monitoring the Antitumor Response of Naive and Memory Cd8 T Cells in Rag1-/- Mice by Positron-emission Tomography.. J. Immunol. Apr 2006;176:4459-67
Abstract
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.
Mesh Headings (Keywords): Animals, CD8-Positive T-Lymphocytes, Female, Homeodomain Proteins, Immunologic Memory, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasms, Phenotype, Positron-Emission Tomography, Stem Cells
Check for Full Text / PubMed Unique Identifier (PMID): 16547284
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