IL-2 during in vitro priming promotes subsequent engraftment and successful adoptive tumor immunotherapy by persistent memory phenotypic CD8(+) T cells

Adoptive T cell tumor immunotherapy potentially consists of two protective components by the transferred effector cells, the immediate immune response and the subsequent development of memory T cells. The extent by which adop tively transferred CD8(+) CTL are destined to become memory T cells is ambi guous as most studies focus on the acute effects on tumor shortly following adoptive transfer. In this study we show that a substantial fraction of th e input CTL develop into memory cells that reject a s.c. tumor challenge. T he use of exogenous IL-2 or a combination of IL-2 and IL-4, but not solely IL-4, during the ex vivo culture for the CTL inoculation was necessary for efficient development of CD8(+) memory T cells. Thus, an important componen t of adoptive immunotherapy using CTL is the production of CD8(+) Ag-specif ic memory cells which is primarily favored by IL-2 receptor signaling durin g ex vivo generation of the effector CTL.