Human T cell immune surveillance: Phenotypic, functional and migratory heterogeneity for tailored immune responses

- The vast majority of human T cells is sequestered in peripheral tissues and remains poorly characterized until now.
- The co-existence of TRM with TEM cells in peripheral tissues suggests a so far unresolved division of labour between both T cell compartments.
- The original markers of tissue resident T cells, CD69 and CD103, do not cover the heterogeneity of tissue resident T cells.

The human immune system constantly provides a balance between pathogen clearance as well as tolerance for autoantigens and the commensal microbiota. This is achieved by immune responses, which are highly specialized and diversified in terms of their phenotype, function, regulation and location. Despite the complexity that is inherent to human immunity, our current knowledge is primarily shaped by very reductionist insights gained from peripheral blood T cells. Since only 2% of human T cells recirculate in the blood, the vast majority remains undetected by common sampling strategies and therefore unexplored. This review highlights and discusses recent developments in human T cell immune surveillance with a particular focus on functional and migratory T cell heterogeneity and provides a critical framework for new conceptual ideas, which could serve as a starting point in the quest for novel targeted therapies for chronic tissue restricted inflammatory diseases.