A primary role for human central memory cells in tissue immunosurveillance

Abstract

Central memory T cells (T_CM) patrol lymph nodes, providing central immunosurveillance against known pathogens, but have not been described as conducting primary tissue immunosurveillance. We analyzed the expression of tissue-homing addressins in human T_CM vs effector memory T cells (T_EM) from the same donors. In humans, the majority of human T_CM were tropic for either skin or gut, and the overall tissue tropism of T_CM was comparable to that of T_EM T_CM were present in healthy, noninflamed human skin, lung, colon, and cervix, suggesting a role for T_CM in the primary immunosurveillance of peripheral tissues. T_CM also had potent effector functions; 80% of CD8⁺ T_CM produced TC1/TC2/TC17/TC22 cytokines. T_CM injected into human skin-grafted mice migrated into skin and induced inflammatory eruptions comparable to T_EM-injected mice. In summary, human T_CM express peripheral tissue-homing receptors at levels similar to their effector memory counterparts, are found in healthy human tissues, have impressive effector functions, and can act alone to induce skin inflammation in human engrafted mice. Our studies support a novel role for human T_CM in primary immunosurveillance of peripheral tissues and highlight the important role of this long-lived cell type in tissue-based immune responses.