Article: article from journal or magazin.
Optimum in vitro expansion of human antigen-specific CD8 T cells for adoptive transfer therapy.
Clinical and experimental immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Increasing evidence suggests that adoptive transfer of antigen-specific CD8(+) T cells could represent an effective strategy in the fight against chronic viral infections and malignancies such as melanoma. None the less, a major limitation in the implementation of such therapy resides in the difficulties associated with achieving rapid and efficient expansion of functional T cells in culture necessary to obtain the large numbers required for intravenous infusion. Recently, the critical role of the cytokines interleukin (IL)-2, IL-7 and IL-15 in driving T cell proliferation has been emphasized, thus suggesting their use in the optimization of expansion protocols. We have used major histocompatibility complex (MHC) class I/peptide multimers to monitor the expansion of antigen-specific CD8 T lymphocytes from whole blood, exploring the effect of antigenic peptide dose, IL-2, IL-7 and IL-15 concentrations on the magnitude and functional characteristics of the antigen-specific CD8(+) T cells generated. We show here that significant expansions of antigen-specific T cells, up to 50% of the CD8(+) T cell population, can be obtained after a single round of antigen/cytokine (IL-2 or IL-15) stimulation, and that these cells display good cytolytic and interferon (IFN)-gamma secretion capabilities. Our results provide an important basis for the rapid in vitro expansion of autologous T cells from the circulating lymphocyte pool using a simple procedure, which is necessary for the development of adoptive transfer therapies.
Adoptive Transfer, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cell Culture Techniques, Cell Division, Cell Line, Dose-Response Relationship, Immunologic, Epitopes, T-Lymphocyte, Humans, Immunophenotyping, Interleukin-15, Interleukin-2, Interleukin-7, Melanoma, Neoplasm Proteins
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