Cell division in the compartment of naive and memory T lymphocytes.

Expression of activation markers and proliferative status were measured in peripheral CD4+ and CD8+ T cells of various T cell receptor (TCR)-transgenic mice either before or after intentional antigenic stimulation. In the absence of intentional immunization, CD4+ T cells persisted as resting or partially activated and cycling cells depending on the specificity of their TCR. Similar results were obtained following transfer into T cell-deficient recipients, i.e. T cells that were not cycling in situ did not cycle after transfer, whereas cells that were proliferating in situ also cycled after transfer. Thus, the TCR of some cells in the absence of intentional antigenic stimulation may bind to some unidentified ligand that does not induce tolerance, but rather slow expansion. In a different sort of experiment, activated T cells that were derived from noncycling naive T cells by deliberate antigenic stimulation continued to cycle slowly even a long time after transfer into antigen-free recipients that did not induce proliferation of the naive cells. Thus, lymphokines or ligands that do not induce activation of naive T cells may be responsible for the maintenance of memory cells. Our experiments show that the latter does not depend on a second TCR expressed by the memory cells, since memory T cells from RAG-2(-/-) TCR-transgenic mice persisted to a similar extent.