CD8+ T Cells Are the Effectors of the Contact Dermatitis Induced by Urushiol in Mice and Are Regulated by CD4+ T Cells

Abstract

Background: The exposure of human skin to leaves and branches of litre (Lithraea caustica), a Chilean endemic tree, induces a severe contact dermatitis characterized by swelling and pruritus in susceptible individuals. The allergenic priniciple of litre is 3–pentadecyl (10–enyl) catechol (litreol), which is structurally similar to the allergens isolated from poison oak and poison ivy. All of them belong to a family of compounds named urushiols. As a proelectrophilic allergen, litreol must be intracellularly activated before modifying proteins of individuals exposed to it. As a result, self–peptides derived from litreol–modified intracellular proteins would be presented in the context of class I MHC molecules. We hypothesized that CD8+ T lymphocytes would play a major role during the effector phase of the immune response induced by those modified peptides. In order to test this hypothesis, we investigated the cellular immune response to litreol in Balb/cJ mice. The role of the different lymphocyte subpopulations in this response was assessed by immunodepleting mice of CD4+ or CD8+ T lymphocytes using specific monoclonal antibodies (mAbs). We report the observation that the contact dermatitis induced by litreol has two components: a primary response which does not require TCRαβ+ T cells, and a secondary response mediated mainly by CD8+ T cells and regulated by CD4+ T cells. Our results show that CD8+ lymphocytes play a central role as effectors of the secondary response to litreol. Furthermore, our data suggest that two functionally different CD4+ T subpopulations serve as regulators of the CD8+ T cell function: a CD4+ T helper population sensitive to a low dose of the depleting mAb, and CD4+ T suppressor population which is eliminated only with a high dose of depleting mAb.

Skin Inflammation During Contact Hypersensitivity Is Mediated by Early Recruitment of CD8+ T Cytotoxic 1 Cells Inducing Keratinocyte Apoptosis

“…Although both clinical and experimental studies have suggested roles for CD4 ϩ and CD8 ϩ T cells as the effector T cells mediating CHS (4,5,7,8), studies from this and other laboratories have indicated that: 1) CD8 ϩ Tc1 cells are effector cells in CHS responses in mice (2,3,5,9,10) and in humans (5,11); and that 2) CD4 ϩ Th2/Treg cells regulate the magnitude of CHS (2,3,5,(12)(13)(14)(15).…”

MMP19 Is Essential for T Cell Development and T Cell-Mediated Cutaneous Immune Responses

“…CD8 + T cells appear to be key effectors of CHS, since depletion of CD8 + T cells reduce CHS while MHC class II-deficiency leads to enhanced response [26]–[31]. CD4 + T cells have a prominent role in the resolution and downregulation of CHS [24], [32], [33].…”

Polymerized Urushiol of the Commercially Available Rhus Product in Korea

“…Urushiol, an antigen of rhus, acts as a hapten and exhibits antigenicity, binding with self-protein 4,5 . Urushiol is a catechol complex that is comprised of either a C15 or C17-alkyl or alkenyl group on the side chain.…”

“…Urushiol, the sap of the Japanese lacquer tree, is the active immunogen of rhus. Urushiol, acting as hapten, binds with selfprotein to then generate neo-antigenic determinants 4,5 . The principle of current rhus poison detoxification techniques is the elimination of urushiol.…”