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 functional memory T cells. Using a MHC-compatible adoptive transfer system, we show here that a short, 3-day IL-4 but not IL-2 or IL-12 exposure during in vitro T cell receptor stimulation of naive CD8(+) T cells induced long-lasting in vivo memory. Such long-term memory CD8(+) T cells expressed antigen-specific cytotoxicity and the potential for IFN-gamma and IL-4 production. Our results support the concept that functional T cell longevity can be regulated by cytokines during initial antigen encounter and provide a rational foundation for vaccine development. They also may have implications in formulating optimal therapeutic regimens of ex vivo expanded autologous cancer- and HIV-specific CD8(+) T cells. In addition, the availability of large numbers of memory CD8(+) T cells generated through our high-efficiency system should facilitate progress in the molecular dissection of CD8(+) T cell memory development.
Huang
L R
LR
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Republic of China.
Chen
F L
FL
Chen
Y T
YT
Lin
Y M
YM
Kung
J T
JT
D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D017931:DNA Primers; D007156:Immunologic Memory / Q000187:drug effects*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects* / Q000276:immunology
D017931:DNA Primers; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4