Stability of naive and memory phenotypes on resting CD4 T cells in vivo

The reliable identification of naive and memory CD4 T cells is critical to understanding the cellular basis of immunological memory, However, it has l ong been a controversial issue whether naive and memory phenotypes are stab le among resting CD4 T cells in the absence of overt stimulation or whether the proposed memory phenotype is a transient, reversible one that represen ts recently activated cells. In this study, adoptively transferred, purifie d populations of naive or memory phenotype CD4 T cells are monitored over t ime to assess the stability of phenotypes and the functional capabilities o f transferred cells. Studying both TCR transgenic and nontransgenic CD4 T c ell populations allows one to control for the capacity to respond to enviro nmental Ags in vivo. Several findings are reported. The first is that in th e absence of Ag, both naive and memory phenotypes remain unchanged over tim e, Second, when changes are seen in populations of transferred naive phenot ype CD4 T cells, they take place only when there is a potential for antigen ic challenge, suggesting that it is an Ag-driven event. Furthermore, when a change from naive to memory phenotype is observed, these transferred donor cells also function as memory cells. Third, the ability of memory CD4 T ce lls to retain the memory phenotype is independent of specific Ag.