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Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center [H-M. H., C. H. P., W. J. U., B. A. F.], Portland, Oregon 97213, and Departments of Biochemistry and Molecular Biology [H-M. H., B. A. F.] and Molecular Microbiology and Immunology [B. A. F.], Oregon Health and Science University, Portland, Oregon 97201
When naïve T cells reconstitute lymphopenic hosts, they transiently proliferate and differentiate into memory-like T cells. Here we report that tumor-specific T cells preferentially expand in tumor vaccine-draining lymph nodes after a melanoma vaccine given to RAG1 mice reconstituted with naïve T cells from normal mice. The percentage of tumor-specific Tc1 T cells detected by intracellular cytokine staining was increased 
4-fold in reconstituted lymphopenic hosts compared with normal hosts. Concomitantly, vaccination-induced Th1 T cells were also dramatically increased in vaccinated, reconstituted RAG1 hosts. T cells derived from reconstituted RAG1 hosts exhibited a higher level of melanoma-specific cytotoxicity in vitro. These cells were significantly more potent at mediating tumor regression in vivo after adoptive transfer into mice bearing established pulmonary metastases. Vaccination is best performed concomitantly with reconstitution; delayed vaccination resulted in T cells with less therapeutic activity.
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