Yuichi Teraki1, Tetsuo Shiohara. 1. Department of Dermatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
Abstract
BACKGROUND: Although effector and regulatory T cells play roles in the progression and resolution of inflammatory diseases, respectively, little in vivo data exist regarding the T-cell dynamics in the pathogenesis of inflammatory skin diseases in humans. OBJECTIVE: Our aim is to phenotypically and functionally characterize the T cells responsible for initiation and regulation of inflammatory events in fixed drug eruption (FDE) as a disease model to study the role of cytokines produced within the epidermis in the pathogenesis of inflammatory skin disease. METHODS: By use of flow cytometry, we phenotypically and functionally characterized the intraepidermal T cells that persist as a stable population in resting (pigmented) FDE lesions and that are present in active FDE lesions. RESULTS: In resting FDE lesions, most of the intraepidermal T cells were of the CD8 phenotype, most of which expressed cutaneous lymphocyte-associated antigen, alpha4beta1, CD11a, alphaEbeta7, and CD45RA but not CD27, CD62L, CCR4, or CCR7. This population selectively expressed CD122 but not CD25. Intracellular staining demonstrated that most intraepidermal CD8+ T cells were capable of producing IFN-gamma and TNF-alpha but produced little IL-2 and IL-4. On the other hand, in the FDE lesions that arose after challenge, a significant number of CD4+ T cells capable of producing IL-10 migrated into the lesional epidermis. Moreover, nearly 70% of the CD4+ T cells migrating into the lesional epidermis expressed CD25. CONCLUSIONS: Effector IFN-gamma-producing CD8+ T cells and regulatory IL-10-producing CD4+ T cells might be responsible for the progression and resolution of FDE, respectively.
BACKGROUND: Although effector and regulatory T cells play roles in the progression and resolution of inflammatory diseases, respectively, little in vivo data exist regarding the T-cell dynamics in the pathogenesis of inflammatory skin diseases in humans. OBJECTIVE: Our aim is to phenotypically and functionally characterize the T cells responsible for initiation and regulation of inflammatory events in fixed drug eruption (FDE) as a disease model to study the role of cytokines produced within the epidermis in the pathogenesis of inflammatory skin disease. METHODS: By use of flow cytometry, we phenotypically and functionally characterized the intraepidermal T cells that persist as a stable population in resting (pigmented) FDE lesions and that are present in active FDE lesions. RESULTS: In resting FDE lesions, most of the intraepidermal T cells were of the CD8 phenotype, most of which expressed cutaneous lymphocyte-associated antigen, alpha4beta1, CD11a, alphaEbeta7, and CD45RA but not CD27, CD62L, CCR4, or CCR7. This population selectively expressed CD122 but not CD25. Intracellular staining demonstrated that most intraepidermal CD8+ T cells were capable of producing IFN-gamma and TNF-alpha but produced little IL-2 and IL-4. On the other hand, in the FDE lesions that arose after challenge, a significant number of CD4+ T cells capable of producing IL-10 migrated into the lesional epidermis. Moreover, nearly 70% of the CD4+ T cells migrating into the lesional epidermis expressed CD25. CONCLUSIONS: Effector IFN-gamma-producing CD8+ T cells and regulatory IL-10-producing CD4+ T cells might be responsible for the progression and resolution of FDE, respectively.
Authors: Jason A Trubiano; Kaija Strautins; Alec J Redwood; Rebecca Pavlos; Katherine C Konvinse; Ar Kar Aung; Monica A Slavin; Karin A Thursky; M Lindsay Grayson; Elizabeth J Phillips Journal: J Allergy Clin Immunol Pract Date: 2017-10-31