Cytotoxic T cell response to lymphocytic choriomeningitis virus. Properties of precursors of effector T cells, primary effector T cells and memory T cells in vitro and in vivo.

Spleen cells from CBA/H mice pre-primed intravenously at various intervals with lymphocytic choriomeningitis (LCM) virus were tested for their capacity to respond and generate cytotoxic effector T cells on secondary stimulation both in vitro and in vivo. In vitro secondary stimulation was performed by culturing preprimed spleen cells with infected, syngeneic, peritoneal `stimulator' cells for periods of up to 7 days at 37°. Controls were incubated with uninfected `stimulators'. In vivo secondary stimulation was obtained by intravenous transfer of pre-primed spleen cells into irradiated, heavily infected CBA/H recipients at various times prior to assay of recipients' spleens. Controls were uninfected, irradiated recipients. Effectors were assayed against LCM virus-infected or uninfected, H-2 compatible L929 target cells in a 51Cr release assay. Spleen cells gave three different patterns of cytotoxic T cell response following in vitro or in vivo stimulation, depending upon the interval between priming and secondary stimulation. Populations taken from mice approximately days 2–5 post-infection (PI) developed increasing cytotoxic activity against virus-infected targets in vitro when cultured with infected or uninfected peritoneal cells, or in vivo when transferred into irradiated, uninfected recipients. However, these early populations did not generate cytotoxic activity when transferred into irradiated, heavily infected recipients. Established primary effector populations (i.e. approx. days 7–11 PI) exhibited continuing effector activity when maintained in vitro or in vivo, more so when peritoneal `stimulator' cells or irradiated recipients were infected. Memory populations (i.e. more than approx. day 13 PI) developed highly potent secondary effectors when cultured with infected peritoneal cells, or on transfer to irradiated, infected recipients. The three different patterns of cytotoxic T cell response of the different preprimed spleen cell populations can be interpreted as indicating three different phases of functional activity of the same population of antigen-reactive T cells from LCM virus-primed mice.