The Vast Majority of CLA+ T Cells Are Resident in Normal Skin

Abstract

There are T cells within normal, noninflamed skin that most likely conduct immunosurveillance and are implicated in the development of psoriasis. We isolated T cells from normal human skin using both established and novel methods. Skin resident T cells expressed high levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6. Skin T cells had a remarkably diverse TCR repertoire and were mostly Th1 memory effector cells with smaller subsets of central memory, Th2, and functional T regulatory cells. We isolated a surprising number of nonexpanded T cells from normal skin. To validate this finding, we counted T cells in sections of normal skin and determined that there are ∼1 × 106 T cells/cm2 normal skin and an estimated 2 × 1010 T cells in the entire skin surface, nearly twice the number of T cells in the circulation. Moreover, we estimate that 98% of CLA+ effector memory T cells are resident in normal skin under resting conditions. These findings demonstrate that there is a large pool of memory T cells in normal skin that can initiate and perpetuate immune reactions in the absence of T cell recruitment from the blood.

Immunological memories of the bone marrow

“…In absolute numbers, the human skin harbors almost twice as many CD45RO + T cells as the peripheral blood 160. Human bone marrow contains 3‐4 times as many CD45RO + T cells as peripheral blood 33.…”

“…“Tissue‐resident” memory T cells have downregulated S1PR1, like CD69 + bone marrow memory T cells 33. “Tissue‐resident” memory T cells, despite expressing CD69, rest in terms of proliferation and expression of effector molecules 160, 163. “Tissue‐resident” memory CD8 + T lymphocytes have a typical gene expression signature, and express the transcription factor Hobit 134, 159.…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Consequently, the skin is an important ''lymphoid organ,'' as the skin contains twice as many T cells ( 20 billion) than the peripheral blood [15]. Following antigenic activation, naïve T cells differentiate into effector and memory cells with distinct migratory patterns characterized by the expression of tissue-specific homing addressins.…”

“…Following antigenic activation, naïve T cells differentiate into effector and memory cells with distinct migratory patterns characterized by the expression of tissue-specific homing addressins. The overwhelming majority of skin-resident T cells are CD45RO 1 memory T cells expressing the skin-homing addressin CLA, which binds E-selectin on post-capillary venules in the skin and is required for lymphocyte rolling [15]. Skin-resident T cells highly express the chemokine receptors CCR4, CCR6, and CCR10, among others, required for their migration into the skin [15][16][17].…”

“…The overwhelming majority of skin-resident T cells are CD45RO 1 memory T cells expressing the skin-homing addressin CLA, which binds E-selectin on post-capillary venules in the skin and is required for lymphocyte rolling [15]. Skin-resident T cells highly express the chemokine receptors CCR4, CCR6, and CCR10, among others, required for their migration into the skin [15][16][17]. In contrast to central memory T cells (T CM ) expressing CCR7 and L-selectin, required for lymph-node homing and circulation in the peripheral blood, effector memory T cells (T EM ) form a persistent population of tissue-resident cells capable of rapidly responding to antigenic rechallenge and comprise 80% of T cells residing in normal skin [15].…”