Differential stimulatory requirements and regulation of naive and primed human lymphocytes

In these investigations, human lymphocytes primed in vitro in MLR have been employed as a model for human memory cells and have been compared to naive lymphocytes from the same donor. Both the stimulatory requirements and the regulation of these cells were found to differ significantly. The dose of stimulators giving a maximal primary (I°) response was < 10% the dose of restimulating cells giving a maximal secondary (II°) response, II° responses were further found to be inversely related to the original I° response. This was associated with at least two separate regulatory phenomena. Suppressor cell induction was enhanced at high priming doses while memory cell precursors were preferentially stimulated at very low priming doses. Priming of memory cells could also be demonstrated to occur in the absence of any detectable I° proliferation by utilizing platelets or heat treated stimulators. Memory cells were also a much more resistant than naive cells to both alloantigen induced suppressor cells and to culture activated monocyte suppressor cells. This in vitro model suggests that the human I° and II° responses to alloantigen have both distinct triggering requirements and differential sensitivity to regulatory cells. It is suggested that preferential formation of memory cells under conditions that require no proliferation and which are suboptimal for suppressor cell generation and the acquired resistance of memory cells to down regulation by suppressor cells may contribute to the poor graft prognois of sensitized renal transplant patients.