Search PubMed⌕ Search

Biomedical subjects

T Shiohara

Publications and source records attributed to T Shiohara.

At least 73 records · Page 4Linked to original sources
PubMed1994

Drug-induced expression of intercellular adhesion molecule-1 on lesional keratinocytes in fixed drug eruption.

The mechanism(s) and the factor(s) that contribute to preferential localization of fixed drug eruption (FDE) lesions to certain skin sites remain speculative. Previous studies suggested that populations of T cells residing in the lesional epidermis may be involved in selective destruction of the epidermis in FDE. In this study, to define the earliest cellular and molecular events with potential relevance to activation of the epidermal T cells, expression of adhesion molecules on keratinocytes (KC) and vascular endothelium was examined sequentially in the lesional skin of FDE patients after challenge with the causative drug. Rapid and intense intercellular adhesion molecule-1 (ICAM-1) expression was induced on the vascular endothelium and KC as early as 1.5 hours after challenge, at which time E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were not up-regulated. In vitro studies using skin organ culture showed that the lesional KC and endothelium responded more rapidly and intensely to express ICAM-1 to tumor necrosis factor-alpha or interferon-gamma compared with those in the nonlesional skin. Surprisingly, such selective induction of KC ICAM-1 restricted to the lesional skin was also observed after exposure to the causative drug alone in skin organ culture. Pretreatment of the lesional skin with anti-tumor necrosis factor completely abrogated in vitro induction of KC ICAM-1 expression by the drug. Drug-induced, TNF-alpha-dependent KC ICAM-1 expression in the lesional skin suggests that induction of ICAM-1 expression by the lesional KC after ingestion of the drug would probably provide a localized initiating stimulus for activation of the disease-associated epidermal T cells.

Adolescent↗
PubMed1993

Identification of a novel population of CD8 alpha+ beta- bone marrow-derived dendritic epidermal cells. This unique population is subsequently outnumbered by thymus-independent expansion of the CD8 alpha+ beta+ dendritic epidermal cells.

Maturation of some T cell populations has been suggested to occur in epithelial tissues. The CD8 molecule, which is expressed as heterodimers made of alpha/beta-chains on virtually all peripheral T cells, is preferentially expressed as homodimers made only of alpha-chains on a subset of CD8+ mouse gut intraepithelial lymphocytes, which arise from bone marrow (BM) precursors in a thymus-independent mechanism. This unique population of CD8 alpha+ beta- T cells, however, has not been identified in other lymphoid tissues in normal adult mice. Because our previous study demonstrated that reconstitution of thymectomized irradiated mice with T cell-depleted BM cells resulted in the appearance of CD8+, TCR-alpha beta+ dendritic epidermal cells (DEC) and suggested that a proportion of the BM-derived DEC may mature within the epidermis, we asked whether the unique phenotype of CD8 alpha+ beta- could be detected among the CD8+ BM-derived DEC. In this report for the first time we identified this unique population of CD8 alpha+ beta- cells among the DEC. Although this population comprised the predominant fraction of the BM-derived DEC in the early post-transfer period (2 to 3 mo), gradual shift from the CD8 alpha+ beta+ phenotypes occurred during the late post-transfer period (4 to 6 mo) independently of the presence of the thymus. Kinetic studies on the BM-derived DEC revealed that this phenotypic shift could be caused by the subsequent expansion of the CD8 alpha+ beta+ DEC. In contrast, the CD8 alpha+ beta- population was the major subset of the BM-derived intraepithelial lymphocytes throughout the entire observation period and the phenotypic shift with age was never observed. These results indicate that CD8 alpha+ beta- cells are preferentially detected on T cells that home to the epithelial tissues and that in the epidermis, but not in the gut epithelia, the subsequent expansion of the CD8 alpha+ beta+ DEC would dilute the high number of the CD8 alpha+ beta- cells.

Animals↗
PubMed1993

Cytotoxic T cell responses to minor H-43 alloantigens in H-43a and H-43b mice. Distinctive MHC class I restriction specificity and clonal inactivation are inherent properties of the H-43 system.

Our previous studies demonstrated that CTL responses to the newly identified minor H-43a and H-43b alloantigens induced in H-43b and H-43a responder mice, respectively, utilized the same H-2Kb (Kb) MHC class I restriction element, whereas many allelic class I products were not utilized. Also, a single i.v. injection of H-43b recipient mice with spleen cells (SC) from H-43 congenic mice induced specific and lasting CTL tolerance to H-43a rather than priming. We have produced a H-43b C3H.AU mouse strain (H-2p), which we regard as H-43 congenic to the C3H.NB (H-2p, H-43a) strain. Using this strain we demonstrate that Kp and/or Dp alleles can serve as class 1 restricting elements in the CTL responses to H-43a and H-43b alloantigens. Injection of H-43a recipient mice with antigenic H-43b SC from the paired H-43 congenic abrogated the anti-H-43b CTL response, irrespective of MHC class I specificity, i.e., in the contexts of Kb and of Kp and/or Dp elements. A corresponding result was obtained upon injection of H-43b recipient mice with congenic H-43a SC. The tolerance-inducing capacity of H-43a congenic SC was so strong that injection of these cells into H-43b responders that had previously received immunogenic H-43a SC completely blocked the previously activated Kb-restricted memory CTL activity specific for the H-43a alloantigen.

Animals↗
PubMed1993

Bone marrow-derived dendritic epidermal T cells express T cell receptor-alpha beta/CD3 and CD8. Evidence for their extrathymic maturation.

The majority of murine Thy-1+ dendritic epidermal T cells (DETC) express virtually identical TCR encoded by V gamma 5 and V delta 1 genes and are derived from early fetal thymic precursors. However, not consistent with this notion is an early finding that DETC arise continuously from bone marrow (BM) precursors by a thymus-independent mechanism. To address this issue, donor-type DETC were characterized in lethally irradiated mice that were reconstituted by Thy-1-disparate BM cells with or without a thymus. The BM-derived DETC, unlike their normal TCR-gamma delta counterparts, were found to express the TCR-alpha beta/CD3 complex and CD8, and their migration to the epidermis dermis occurred independently of the thymus. The numbers of the BM-derived DETC increased with time and reached a plateau 6 mo after BM transfer, at which time the TCR-alpha beta/CD3 complex was expressed on a small fraction of the DETC in athymic BM chimeras. Although no further increase in the number was observed at later times, at 1 yr after transfer most of the BM-derived DETC came to express the TCR-alpha beta/CD3 complex in the absence of thymic influence. By contrast, most of BM-derived T cells in other lymphoid organs from athymic BM chimeras still failed to express the TCR-alpha beta/CD3 complex even at 1 yr after transfer. These results suggest that extrathymic differentiation of BM-derived DETC could occur with the epidermal microenvironment.

Animals↗
PubMed1993

Is sustained production of tumor necrosis factor-alpha relevant to the development of pustular psoriasis?

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as one of the critical mediators of psoriasis. Evidence for an important role on the progression of the disease is increasing, while recent clinical studies have suggested its beneficial role in the disease. Based on the results of our sequential analysis of the serum cytokine levels in a patient with pustular psoriasis, we speculate that immunologic effects of constitutive local release of TNF-alpha may be quite different from those of its systemic injection.

Granulocyte-Macrophage Colony-Stimulating Factor↗
PubMed1993

Eosinophilic pustular folliculitis (Ofuji's disease). Immunohistochemical analysis.

BACKGROUND: Eosinophilic pustular folliculitis is a distinctive dermatosis that was first described in Japan. Although the histopathologic feature of eosinophilic pustular folliculitis is characterized by follicular infiltrates with numerous eosinophils, its pathophysiology remains unclear. The lesional skin of five patients with eosinophilic pustular folliculitis was examined using several monoclonal antibodies including a variety of anti-leukocyte adhesion molecules: endothelial cell adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1, by means of immunohistochemical techniques. OBSERVATION: Intercellular adhesion molecule 1 expression by keratinocytes was observed on follicular epithelium, but not on epidermis. The migration of eosinophils and lymphocytes, which were intensely positive for antilymphocyte function-associated antigen 1, was limited to follicular epithelium. Endothelial cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression of vascular endothelium was more often observed around hair follicles. There was no reactivity for interleukin 8 in follicular epithelium. CONCLUSIONS: These findings may explain the selective migration of eosinophils and lymphocytes to the hair follicles in eosinophilic pustular folliculitis.

Adult↗
PubMed1992

Linear IgA bullous dermatosis associated with rheumatoid arthritis.

A case of linear IgA bullous dermatosis associated with rheumatoid arthritis is described. The eruption consisted of multiple irregular erythematous plaques and small numbers of tense vesicles mainly on the trunk. An immunofluorescence study showed linear IgA and IgG deposition along the basement membrane zone, whereas C3 deposition was not found. IgA or IgG anti-basement membrane zone antibody was not detected in the serum. Treatment with dapsone resulted in good control of the eruption. Coexistence of linear IgA bullous dermatosis and rheumatoid arthritis has not been reported previously.

Aged↗
PubMed1992

Differential effects of cyclosporine and etretinate on serum cytokine levels in patients with psoriasis.

BACKGROUND: The in vivo effects of cyclosporine and etretinate on the immune system are still unclear. OBJECTIVE: Our purpose was to determine the effects of these drugs on in vivo production of various cytokines. METHODS: Serum cytokine levels were measured sequentially by radioimmunoassay in psoriasis patients treated with either cyclosporine or etretinate. RESULTS: Interferon-gamma levels were initially elevated and rapidly returned to baseline levels before clinical improvement in both treatment groups. A transient increase before the relapse was also observed in some patients. Etretinate treatment resulted in a substantial decrease in tumor necrosis factor-alpha levels, whereas an unpredictable increase was found during the late phase of cyclosporine treatment. CONCLUSION: The in vivo effects of antipsoriatic drugs on cytokine production are different from those demonstrated in vitro. Measurement of serum cytokine levels is useful for monitoring patients with psoriasis.

Administration, Oral↗
PubMed1992

In utero treatment with monoclonal antibody to IL-2 receptor beta-chain completely abrogates development of Thy-1+ dendritic epidermal cells.

Interleukin-2 (IL-2), a crucial growth factor for mature T lymphocytes, is produced in fetal thymus under developmental control, although its biological significance remains unclear. We found that the two distinct subunits of the IL-2 receptor, i.e. the alpha-chain (IL-2R alpha) and the beta-chain (IL-2R beta), were expressed in an almost mutually exclusive fashion throughout fetal thymus ontogeny, and that the blockade of IL-2R beta, a signal transducing component of IL-2R, by administering a neutralizing mAb to IL-2R beta resulted in the complete and selective disappearance of Thy-1+ skin dendritic epidermal cells. Development of any other T cell subsets was uncompromised. This indicates that IL-2 plays a crucial role in the development of fetal V gamma 5+ cells and their descendants.

Animals↗
PubMed1991

Evidence for involvement of lymphocyte function-associated antigen 1 in T cell migration to epidermis.

Although it is well known that in various T cell-mediated skin diseases T cells migrate preferentially to epidermis, no direct evidence has been presented in which molecules on T cells are important in directing T cell traffic to epidermis. We have previously established CD4+ autoreactive cloned T cells with a special tropism for epidermis in vitro as well as in vivo. Antibody inhibition studies demonstrated that only anti-lymphocyte function associated Ag 1 (anti-LFA-1) mAb completely inhibited the in vitro migration of the T cells toward the epidermis, whereas mAb against other T cell surface molecules had little or no effect. Monovalent F(ab) fragment of the anti-LFA-1 mAb, although less efficient, also inhibited the T cell migration. The apparent dependency of the inhibition on the anti-alpha-chain mAb suggested a major role for the alpha-chain of LFA-1 in T cell migration to epidermis. The relevance of an LFA-1-dependent mechanism to the epidermotropic migration of T cells was further strengthened by the findings that the T cell migration to epidermis was inhibited by divalent cation depletion, cytochalasin B, and low temperature. These findings indicate that the LFA-1 molecule, which is thought to be primarily involved in cell-to-cell adhesions, also plays an important role in directing T cell migration to epidermis.

Animals↗
PubMed1991

Prurigo pigmentosa: role of ICAM-1 in the localization of the eruption.

Immunohistochemical studies were carried out on the skin lesions of two cases of prurigo pigmentosa. There was a predominance of CD4+ cells in the dermal infiltrate, whereas those lymphocytes in the epidermis were mainly CD8+ cells. The majority of dermal and epidermotropic lymphocytes showed an intense expression of lymphocyte function-associated antigen 1 (LFA-1). The number of CD1+ cells was increased in the epidermis. There was intense expression of ICAM-1 by keratinocytes in the erythematous papules. Focal expression of ICAM-1 was still observed in the residual pigmented areas and could explain the recurrence of the lesions at these sites.

Adult↗
PubMed1991

Interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma in psoriasis.

Although recent studies have suggested that a variety of cytokines released by keratinocytes and inflammatory leukocytes could contribute to induction or persistence of the inflammatory processes in psoriasis, it remains unclear how production of these cytokines is regulated in psoriatic patients. To elucidate the biologic relevance of these cytokines to the pathogenesis of psoriasis, we investigated serum levels of interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma in 21 patients with psoriasis vulgaris, together with 21 healthy controls. The mean serum levels of interleukin 1 alpha and tumor necrosis factor alpha were not significantly different from those in controls, while those of interferon gamma were significantly elevated in the patients with psoriasis. Serum levels of interleukin 1 alpha correlated negatively with clinical disease severity expressed as psoriasis area and severity index score and with duration of psoriasis. In contrast, interferon gamma levels were related, although not significantly, to disease severity. In addition, an inverse correlation was noted between the interleukin 1 alpha levels and interferon gamma levels. These results indicate that interleukin 1 alpha and interferon gamma may be relevant to the induction and perpetuation, respectively, of the inflammatory responses in psoriasis, and that these cytokines, which have similar biologic properties, may strictly regulate one another's production in vivo.

Adult↗