Relation of DNA synthesis and suppression to development of memory by T cells

Abstract Parental thymocytes, inoculated into lethally irradiated F1 mice, synthesize DNA in response to the histocompatibility antigens of the reciprocal parent in the F1 cross. The DNA synthetic response is characterized by a 1 to 3 day latent period and a 1- to 2-day period of peak activity which is followed by a sharp decline. Cells transferred to secondary recipients at the time of peak activity in the primary hosts respond only minimally in the spleens of the secondary hosts. Cells transferred 1 day later, when DNA synthetic activity in the primary hosts is sharply curtailed, exhibit striking secondary responsiveness. Thus, the decline in activity in the primary host is not due to the loss of potentially reactive cells from the spleens. It seems more likely that the preceding response creates a suppressive milieu in the primary host. The inability to transfer significant secondary responsiveness with cells harvested at the time of peak activity in primary hosts suggests that the acquisition of memory by these cells requires more than their clonal expansion. The occurrence of an additional differentiational event is suggested by the correlation of a marked increase in memory with the sharp cessation of the primary DNA synthetic response.