Development of antitumor immune responses in reconstituted lymphopenic hosts.
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 approximately 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.
Hu
Hong-Ming
HM
Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon 97213, USA. hhu@providence.org
Poehlein
Christian H
CH
Urba
Walter J
WJ
Fox
Bernard A
BA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D019496:Cancer Vaccines; D018398:Homeodomain Proteins; D014409:Tumor Necrosis Factor-alpha; C064658:RAG-1 protein