Memory CD4 cells do not migrate into peripheral lymphnodes in the absence of antigen

Memory T cells are thought to protect against previously encountered pathogens in part by preferentially recirculating through the lymphoid tissues where they were primed and where challenge with antigen (Ag) is likely to occur. In this study, we examined the distribution of memory CD4 cells after priming, and analyzed their capacity to localize in lymph nodes after transfer to normal and Ag-primed recipients. Immunization induced a high frequency of Ag-specific CD4 cells in the primary response in draining lymph nodes and spleen. Thereafter, the numbers in lymph nodes declined dramatically whereas 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 adoptive transfer to normal recipients and were detected predominantly in the spleen for extended periods, suggesting that recirculation through lymph nodes was limited. Memory cells also did not home to lymph nodes recipients in response to specific Ag, but subsequently, recruitment that could be blocked with monoclonal antibodies to CD44 and LFA-1 and was independent of naive cells did occur. The data indicate that memory and naive CD4 cells can be distinguished on the basis of their patterns of circulation.