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Protective Immunity from Naive CD8⁺ T Cells Activated In Vitro with MHC Class I Binding Immunogenic Peptides and IL-2 in the Absence of Specialized APCs¹

Conrad Hauser^1,*,, Frank Zipprich^3,*, Isabelle Leblond^*, Susanne Wirth^* and Ambros W. Hügin

^* Allergy Unit, Division of Immunology and Allergy, and Department of Dermatology, Hôpital Cantonal Universitaire, Geneva, Switzerland

Ag-specific CTL can protect against tumors and some viral infections and may be useful for adoptive immunotherapy. Here, we show that purified CD8⁺ T cells from naive C57BL/6 mice can be primed in vitro with different immunogenic peptides, which bind to MHC class I gene products, and IL-2 to exhibit specific and MHC-restricted effector function in vitro and in vivo protection against lymphocytic choriomeningitis virus infection and B16.F10 melanoma lung metastases. Limiting dilution assays in the absence of feeder cells with highly purified CD8⁺ T cells from two transgenic mice strains, each expressing a different MHC class I-restricted TCR, indicated that only peptide and IL-2, but not TCR^- cells, were required for the growth of naive CD8⁺ T cells. These alternative minimal requirements for the activation and expansion of specific CD8⁺ T lymphocytes, without the need for professional APC, may be exploited for adoptive immunotherapy.