Cutting edge: Secondary lymphoid organs are essential for maintaining the CD4, but not CD8, naive T cell pool

Despite declining thymic output with age, the peripheral naive T cell pool of an adult animal remains remarkably stable. Therefore, a central question in immunology is how the naive T cell pool is maintained. Here we show tha t the maintenance of the naive CD4, but not CD8, T cell population in the t hymectomized adult mouse is dependent on the presence of secondary lymphoid tissues. This finding is explained by the inability of naive CD4 T cells t o sustain normal levels of the survival molecule Bcl-2 or to undergo homeos tatic proliferation in the absence of secondary lymphoid organs. Thus, naiv e CD4 T cells must traffic through secondary lymphoid organs to maintain a stable CD4 pool while naive CD8 T cells encounter their survival and prolif eration signals outside the organized structures of secondary lymphoid tiss ues.