To understand how memory CD4 T cells are generated we have re-examined the
requirements for continuing antigen stimulation in the generation and persi
stence of this population. We find that specific antigen is only required f
or a short period during the activation of naive CD4 T cells and is not req
uired for memory generation from activated CD4 T cells or for persistence o
f resting memory cells generated by transfer of activated CD4 to adoptive h
osts. Moreover, transfer of activated CD4 T cells to class-II-deficient hos
ts, indicates that TcR-class II major histocompatibility interaction is als
o unnecessary for either the transition from activated CD4 T cell to restin
g memory cells or for persistence over an eight-week period. Thus the signa
ls regulating generation and maintenance of memory are fundamentally differ
ent from those which regulate the expansion of effector CD4 T-cell populati
ons which include antigen itself and the CD4 T-cell autocrine cytokines ind
uced by antigen.