A primary role for human central memory cells in tissue immunosurveillance

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 TEM-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.