Rapid synthesis of IFN-gamma by T cells in skin may play a pivotal role in the human skin immune system.
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.
Hassan-Zahraee
M
M
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Wu
J
J
Gordon
J
J
D002118:Calcium / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D007371:Interferon-gamma; D002118:Calcium