IFN-gamma-producing effector CD8+ T cells and IL-10-producing regulatory CD4+ T cells in fixed drug eruption.
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.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003875:Drug Eruptions / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma