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Biomedical subjects

Tetsuo Shiohara

Publications and source records attributed to Tetsuo Shiohara.

30 records · Page 2Linked to original sources
PubMed2003

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.

Adult↗
PubMed2003

Inhibitory activity of CX-659S, a novel diaminouracil derivative, against the rebound phenomenon following withdrawal of corticosteroid therapy for chronic contact hypersensitivity responses.

BACKGROUND: CX-659S, a newly discovered anti-inflammatory compound, exerts inhibitory effects on chronic contact hypersensitivity responses (CHRs) induced by repeated application with picryl chloride (PC), which is known to mimic many, if not all, events occurring within lesional skin of patients with atopic dermatitis (AD). CX-659S suppresses the expression of mRNA for interleukin (IL)-4 and IL-10 but not that for IFN-gamma, and inhibits serum IgE production in a chronic CHR model. Although topical corticosteroids have been widely utilized in steroid-responsive dermatoses such as AD, their chronic use may be associated with significant side effects. In addition, a rebound phenomenon often occurs after discontinuation of prolonged use of topical corticosteroids, with enhanced production of IgE and Th2 cell cytokines. The purpose of this study was to assess whether CX- 659S inhibits the rebound phenomenon after discontinuation of chronic treatment with prednisolone in a chronic CHR model in mice. METHODS: The efficacy of CX-659S as a sequential therapeutic agent after discontinuation of chronic treatment with prednisolone was tested on PC-treated ears of BALB/c mice with chronic CHR. Effects were quantified by measurements of ear thickness, serum IgE and cytokine mRNA expression. RESULTS: The rebound phenomenon was confirmed after discontinuation of chronic treatment with prednisolone in chronic CHR in mice, i.e. by evidence of flare thickening of the ear, enhanced expression of mRNA for IL-4 and IL-10 and increased serum IgE. Sequentially applied CX-659S suppressed these rebound phenomena with a good cosmetic result. CONCLUSIONS: CX-659S is the first promising compound with inhibitory activity on the rebound phenomenon following withdrawal of corticosteroid therapy without immunosuppression.

Administration, Topical↗
PubMed2002

Direct evidence for interferon-gamma production by effector-memory-type intraepidermal T cells residing at an effector site of immunopathology in fixed drug eruption.

Effector-memory T cells are strategically placed to epithelial tissues to provide frontline immune protection against pathogens. Their detrimental effects, however, have been rarely examined because of difficulty in sampling these T cells in pathological settings. Our previous studies suggested persistence of a similar subset of intraepidermal CD8(+) T cells at high frequencies in the lesions of fixed drug eruption, a localized variant of drug-induced dermatoses. In situ activation of this subset resulting in localized epidermal injury can be traced in the lesions after antigen challenge by paired immunohistochemical staining, reverse transcriptase-polymerase chain reaction in situ, and flow cytometry of dispersed cells. Here we show that effector-memory T cells were greatly enriched in these intraepidermal CD8(+) T cells, but not dermal and circulating counterparts, and that they constitutively express an early activation marker CD69 even before challenge. Surprisingly, a large proportion of these T cells expressed immediate effector function as evidenced by the rapid production of high levels of interferon-gamma in situ with much faster kinetics than their counterparts at the mRNA and protein levels after challenge. This was followed by localized epidermal injury. The intracellular cytokine assay ex vivo shows that the great majority of these dispersed T cells produce interferon-gamma. This study provides the first in situ description of the detrimental effects specifically mediated by effector-memory T cells residing at the effector site of immunopathology.

Biopsy↗
PubMed2002

Atypical bullous disease showing features of both erythema multiforme and bullous pemhigoid.

A 78-year-old man presented with multiple, centrifugal erythema, which tended to coalesce, producing polycyclic configurations. The patient developed an annular, narrow blister that was always visible along the margin of the erythema. Histology of a biopsy specimen revealed hydropic degeneration of basal cells, exocytosis of lymphoid cells, and subepidermal blister with necrosis of individual keratinocytes in the blister roof. Direct immunofluorescence studies showed a weak IgG deposition at the basement membrane zone, in a linear fashion, which was confined to the outer side of the blister. Immunoblotting of the patient's serum with human epidermal extract demonstrated circulating antibodies, which reacted to 230 kDa BP antigen 1. These findings suggest that this case is characteristic of both erythema multiforme and bullous pemphigoid and it seems likely that this condition could be a manifestation of epitope spreading, although the exact process in the development of immunological disturbances could not be elucidated.

Aged↗
PubMed2002

Pathophysiology of fixed drug eruption: the role of skin-resident T cells.

PURPOSE OF REVIEW: Fixed drug eruption is a distinct variant of drug-induced dermatoses characterized by their relapse in the same location after the administration of the causative drug. We have recently shown that intraepidermal CD8+ T cells phenotypically resembling effector memory T cells are greatly enriched in the resting lesions of FDE. Although effector memory T cells have been implicated as the mediators of protection in epithelial tissues, our observation raises an alternative possibility that improper, enhanced or uncontrolled activation of intraepidermal T cells could contribute to severe tissue injury. Until recently, however, their detrimental effects on epithelial tissues have rarely been examined. The focus of this review is on how intra-epidermal T cells originally evolved to protect tissue integrity can exert an opposite action that is deleterious to the host. RECENT FINDINGS: Because those T cells residing in the lesions, upon activation, can rapidly produce large amounts of IFN-gammaepsilon followed by localized epidermal injury, their activation is probably essential for the initiation of deleterious inflammatory responses in the lesions. The activity of these potent effector T cells is therefore carefully controlled to prevent unwanted tissue injury under physiological conditions. A complex interplay of stop and go signals to the skin-resident T cells provides a delicate balance between cell death and survival, thereby determining the degree and outcome of inflammation generated in response to pathogens or antigens. SUMMARY: This consideration may provide important insights into the way in which skin-resident T cells maintain immunological homeostasis in the skin.

Drug Eruptions↗
PubMed2002

Lichen amyloidosus associated with Kimura's disease: successful treatment with cyclosporine.

We describe here a case of a 33-year-old man who had lichen amyloidosus associated with Kimura's disease. In this case, treatment with cyclosporine dramatically improved the lesions of both Kimura's disease and lichen amyloidosus. Although Kimura's disease and lichen amyloidosus are both rare distinct entities, to our knowledge, 11 cases of association of Kimura's disease and lichen amyloidosus have been described previously.

Adult↗
PubMed2002

Trauma-localized fixed drug eruption: involvement of burn scars, insect bites and venipuncture sites.

Little is known about why fixed drug eruption (FDE) lesions initially appear in a particular area of predilection. We describe 2 cases in whom the FDE lesions initially appeared exactly at the same sites of a previous trauma, such as burn scars and insect bites, and at a venipuncture site. The interval between the original trauma and the initial onset of FDE ranged from 2 days to 22 years. These 'trauma-localized' FDE lesions are helpful for our understanding of the mechanisms of FDE and other skin diseases, which often appear in their particular areas of predilection, a finding known as 'recall phenomenon'.

Adult↗