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International Immunology, Vol 10, 1599-1612, Copyright © 1998 by Oxford University Press


ARTICLES

Rapid synthesis of IFN-gamma by T cells in skin may play a pivotal role in the human skin immune system

M Hassan-Zahraee, J Wu and J Gordon
Department of Surgery, McGill University, Montreal, Quebec, Canada.

This study has shown that T lymphocytes with alphabeta TCR present in normal human skin possess unique characteristics which may allow them to fulfil a unique role in skin. It disclosed that unlike T cells from blood, they are devoid of proliferative capacity in response to any ligand including lectins and phorbol esters, and show a diminished Ca2+ flux in response to phytohemagglutinin (PHA). However, despite this apparent lack of reactivity, these cells respond to stimulation by synthesis of IFN-gamma. Furthermore, this response by T cells from the skin differs from that of T cells in blood in its tempo. Whereas IFN- gamma is first detectable in peripheral blood lymphocytes (PBL) 42 h following stimulation, T cells from skin produce IFN-gamma 2.5 h after activation, or 17 times faster. Whereas synthesis persists in PBL for several days, it only lasts in skin T cells for 90 min. This difference in the kinetics is a consequence of differences in the regulation of IFN-gamma synthesis in PBL and skin-derived T cells. Thus, unlike PBL, T cells in intact unimmunized skin or ex vivo express mRNA for IFN- gamma, transcribed in a constitutive manner. Activation of these cells turns on translation of IFN-gamma synthesis directly and at the same time turns off further transcription of the IFN-gamma gene: cessation of IFN-gamma synthesis coincides with the disappearance of IFN-gamma mRNA within 4 h of activation. These observations suggest that this pre- formed mRNA may be solely responsible for the early synthesis of IFN- gamma in skin, determining both the amount and the duration of its synthesis. We propose that these cells may represent the antigen- specific component of a first-line host defence system in human skin. The reported absence of delayed-type hypersensitivity reactivity in patients with a selective deficit of skin T cells supports this conclusion.
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