Memory CD4 cells do not migrate into peripheral lymph nodes in the absenceof antigen

Memory T cells are thought to protect against previously encountered pathog ens in part by preferentially recirculating through the lymphoid tissues wh ere they were primed and where challenge with antigen (Ag) is likely to occ ur. In this study, we examined the distribution of memory CD4 cells after p riming, and analyzed their capacity to localize in lymph nodes after transf er to normal and Ag-primed recipients. Immunization induced a high frequenc y of Ag-specific CD4 cells in the primary response in draining lymph nodes and spleen. Thereafter, the numbers in lymph nodes declined dramatically wh ereas frequencies in the spleen were unchanged, suggesting that memory CD4 cells primarily reside in or recirculate through the spleen. Indeed, memory CD4 cells, unlike naive CD4 cells, failed to home to lymph nodes after ado ptive transfer to normal recipients and were detected predominantly in the spleen for extended periods, suggesting that recirculation through lymph no des was limited. Memory cells also did not home to lymph nodes recipients i n response to specific Ag, but subsequently, recruitment that could be bloc ked with monoclonal antibodies to CD44 and LFA-1 and was independent of nai ve cells did occur. The data indicate that memory and naive CD4 cells can b e distinguished on the basis of their patterns of circulation.