Figure 4. Model for compartmentalization of antigen-specific memory T cell subsets in space and time.

This schematic shows the relative naïve and memory T cell subset frequencies in the circulation and peripheral sites and at different life stages. The schematic also shows the biased specificity for microbial antigens derived from pathogens that has been observed in specific tissue sites, including cytomegalovirus (CMV) in the blood; Epstein-Barr virus (EBV) in the spleen; vaccinia virus in lymph nodes; influenza virus in the lungs; rotavirus in the intestine and herpes simplex virus (HSV) and varicella zoster virus (VZV) in the skin. In addition, the specificities of some memory T cells at mucosal sites (lungs, intestine and skin) are biased for antigens from the microflora. The relative frequencies of each T cell subset in each tissue site for youths through adults are compiled from Ref. 11, and are extrapolated for infants based on Refs. 21, 22. At birth, there is a preponderance of naïve T cells in the circulation, and an abundance of mucosal microbial antigens are encountered during infancy, resulting in seeding of mucosal sites with T_EM cells specific for mucosal pathogens, which could develop into T_RM cells in situ. Infant skin has few, if any T cells (R. Clark, personal communication) and therefore estimates for memory T cell content in skin begin during youth. During childhood, exposure to the ubiquitous pathogenic and non-pathogenic microbial species in each site occurs and new memory T cells are formed which are partitioned as T_RM cells in skin and mucosal sites, and as T_CM cells in lymphoid tissues. This basic partitioning of antigen-specific memory T cell subsets in tissues is maintained during adulthood, with more T_EM and T_CM cell subsets gradually accumulating in the circulation and lymph nodes that could potentially replenish and/or convert to T_RM cells that are lost through attrition.