Production of high titers of interferon-gamma by prestimulated murine spleen cells.

Concanavalin A (Con A)-induced interferon-gamma (IFN-gamma) production by murine spleen cells prestimulated with Con A for different periods of time has been studied. Highest titers of antiviral activity were obtained by restimulation of cells that had been prestimulated with Con A for 3 days. These cells produced up to 30 times more IFN than freshly isolated spleen cells stimulated under the same conditions. In an effort to explain this rise in the capacity to produce IFN-gamma, the possibility that it was due to the inactivation of a suppressor cell was excluded. The addition of freshly isolated spleen cells at different concentrations to prestimulated cells did not affect subsequent Con A-induced IFN-gamma production. Separation of freshly isolated or prestimulated spleen cells by velocity sedimentation at unit gravity showed that in the latter case most of the IFN-gamma was produced by a population of large-sized cells not present in the former population. It was concluded from these experiments that prestimulation of spleen cells with Con A gives rise to a population of large-sized cells that produce, upon restimulation with the same mitogen, much higher titers of IFN-gamma than those obtained upon primary stimulation of small resting lymphocytes.