Abstract C1
Clark R(achael)A, Mollet I(lse), Hijnen D(irkjan), Calarese A(dam), Purwar R(ahul),
Lichtman M(ichael), and Kupper T(homas)S. Skin resident T cells producing TNF but not
Th1, Th2, or Th17 cytokines: their possible role as immune sentinels in skin. J Invest
Dermatol. (2009) 129 (Suppl 1): S110
TITLE: Skin resident T cells producing TNFα but not Th1, Th2, or Th17 cytokines:
their possible role as immune sentinels in skin
AUTHORS (FIRST NAME INITIAL LAST NAME): R. A. Clark1, I. Mollet1, D.
Hijnen1, A. Calarese1, R. Purwar1, M. Lichtman1, T. S. Kupper1
INSTITUTIONS (ALL): 1. Department of Dermatology, Brigham and Women's Hospital,
Boston, MA, USA.
ABSTRACT BODY: The skin of a normal individual contains nearly 20 billion memory T
cells, nearly twice as many as are present in the circulation. These T cells are polarized
effector memory T cells that, from our current understanding, have arisen from recognition of
their antigens within the skin. We previously reported that human skin contains significant
numbers Th1, Th17 and Th2 cells. We report now that these T cell subsets are quiescent with
respect to cytokine production when isolated from unstimulated skin and that additional
signals (e.g., cellular proliferation) are required to unlock cytokine production. TNFα is a
cytokine produced by both APC and subsets of effector T cells. We describe here a novel and
previously undescribed population of skin resident T cells that produces TNFα alone, without
concurrent production of IFNγ, IL-4 or IL-17. These cells comprise a mean 48% of the skin T
cells resident in normal human skin. These T cells are CD45RO+ memory T cells, express
CLA, CCR4 and CCR6 and have a diverse TCR repertoire. This T cell subset differs from the
other cutaneous effector T cells in that half of these cells produce TNFα upon TCR triggering
without a requirement for additional activating signals. TNFα T cells are the most numerous
subset in normal human skin, outnumbering Th1, Th2 and Th17 T cells. TNFα has pleiotropic
effects in the skin. TNFα induces maturation of dendritic cells, enhancing antigen
presentation, and induces endothelial activation and chemokine production, leading to
enhanced leukocyte recruitment. Skin TNFα T cells, specific for pathogens previously
encountered in skin, may serve as antigen-specific immune sentinels. These T cells have the
ability to rapidly produce TNFα upon re-exposure to cognate antigen, leading to activation
and recruitment of both innate immune cells and other T cell subsets. Thus, they may serve to
both initiate and amplify immune responses in skin.