Mark V. Dahl, MD 

Understanding the development of long-lived skin resident T cells

Interaction of a “naïve” T lymphocyte with an appropriately presented antigen induces a primary cell–mediated immune response. If the antigen is encountered in skin, the naïve T cells in lymph nodes become effector memory T cells. They then upregulate skin-homing addressins, migrate into skin, and, with any luck, work there to destroy persistent threatening antigens, such as those associated with infectious agents. After the battle is finished, the skin contains many tissue-resident memory T cells (TRM cells), even in skin that never encountered the antigen. These skin-resident memory cells stay in skin to establish an on-site defense against similar antigens that might breach the skin barrier at some future date. However, other, phenotypically different effector cells remain in the blood as central memory T cells (TCM), which express lymph node–homing addressins. They reinforce the defenses of skin-resident T cells with their ability to rapidly multiply, to rapidly become effector T cells after antigen challenge, and to rapidly migrate into tissues. So, the “front-line” skin-resident T cells reside on site in skin for immediate response, and “behind-the-line” TCM cells reside in blood to reinforce defense, both locally and systemically.

These investigators recently discovered how skin-resident T cells changed after entering the skin as epithelium-infiltrating effector memory T cells (TEM cells). To become a functioning, long-lived skin-resident T cell, the cell has to infiltrate into skin, express CD103+ and CD8+, and respond to local signaling by interleukin 15 and transforming growth factor-β. In skin, these cells now have unique transcriptional profiles. They have “grown up” in the skin.

Citation(s):

Mackay LK et al. The developmental pathway for CD103+ CD8+ tissue-resident memory cells of skin. Nat Immunol 2013 Dec; 14:1294.