Author(s) : Pierre SAINT-MEZARD, Aurore ROSIERES, Maya KRASTEVA, Frédéric BERARD, Bertrand DUBOIS, Dominique KAISERLIAN, Jean-François NICOLAS , INSERM U 503, IFR 128 Bioscience Lyon-Gerland, 21, avenue Tony Garnier 69007 Lyon, INSERM U 404, IFR 128 Bioscience Lyon-Gerland, 21, avenue Tony Garnier 69007 Lyon, Clinical Immunology and Allergy Unit, CH Lyon-Sud, 69495 Pierre-Benite Cedex, France., J.F. Nicolas, Fax: (+33) 478 861 528. E-mail: jean-francois.nicolas@chu-lyon.fr.
Summary : Contact dermatitis is an inflammatory skin condition induced by exposure to an environmental agent. Eczema and dermatitis are used synonymously to denote a polymorphous pattern of skin inflammation characterized at least in its acute phase by erythema, vesiculation and pruritus. Substances responsible for contact dermatitis after single or multiple exposures are non protein chemicals, i.e. haptens, that induce skin inflammation through activation of innate skin immunity (irritant contact dermatitis) or both innate and acquired specific immunity (allergic contact dermatitis). The present review will focus on allergic contact dermatitis, a delayed-type hypersensitivity reaction, which is mediated by hapten-specific T cells. Recent advances in the pathophysiology of ACD have shown that the occurrence of ACD, as well as its magnitude and duration, is controlled by the opposite functions of CD8 effector T cells and CD4 regulatory T cells. From these studies ACD can be considered as a breakdown of cutaneous immune tolerance to haptens.
Keywords : haptens, CD8 T cells, CTL, CD4 regulatory T cells, tolerance, contact sensitivity, contact dermatitis
Pictures
Figure 1 Pathophysiology of CHSSensitization
step: Haptens penetrate the stratum corneum. Hapten loading by
skin dendritic cells (step 1) parallels activation and migration of
DC through the afferent lymphatic vessels to the draining lymph
nodes (step 2). Migrating DC are located in the para-cortical area
of the draining LN where they can present haptenated peptides on
MHC class I and II molecules to CD8+ and CD4+ T cells, respectively
(step 3). Specific T cells precursors expand clonally in the
draining LN and diffuse to the bloodstream through the efferent
lymphatic vessels and the thoracic duct (step 4). During this
process they acquire skin-specific homing antigens (CLA and CCR4)
and become memory T cells. Primed T cells preferentially diffuse in
the skin after transendothelial migration. At the end of the
sensitization step everything is ready for the development of a CS
reaction upon challenge with the relevant hapten.Elicitation
phase: When the hapten is painted for a second (and subsequent)
time, it diffuses through the epidermis and could be loaded by LC
or other skin cells expressing MHC molecules, such as keratinocytes
and dermal dendritic cells, which are then able to activate
trafficking specific T cells (step 5). CD8+ cytotoxic T cell
activation initiates the inflammatory process through keratinocyte
apoptosis and cytokine/chemokine production (step 6). This is
responsible for the recruitment of leukocytes (including regulatory
T cells) from the blood to the skin leading to the development of
skin lesions (step 7).
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