Potent induction of long-term CD8(+) T cell memory by short-term IL-4 exposure during T cell receptor stimulation

An important goal of vaccination is to achieve long-term survival of functi onal memory T cells. Using a MHC-compatible adoptive transfer system, we sh ow here that a short, 3-day IL-4 but not IL-2 or IL-12 exposure during in v itro T cell receptor stimulation of naive CD8(+) T cells induced long-lasti ng in vivo memory. Such long-term memory CD8(+) T cells expressed antigen-s pecific cytotoxicity and the potential for IFN-gamma and IL-4 production. O ur results support the concept that functional T cell longevity can be regu lated by cytokines during initial antigen encounter and provide a rational foundation for vaccine development. They also may have implications in form ulating optimal therapeutic regimens of ex vivo expanded autologous cancer- and HIV-specific CD8(+) T cells. in addition, the availability of targe nu mbers of memory CD8(+) T cells generated through our high-efficiency system should facilitate progress in the molecular dissection of CD8(+) T cell me mory development.