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T Shiohara

Publications and source records attributed to T Shiohara.

At least 91 records · Page 5Linked to original sources
PubMed1990

Loss of epidermal integrity by T cell-mediated attack induces long term local resistance to subsequent attack. II. Thymus dependency in the induction of the resistance.

Our previous study showed that in cutaneous graft-vs-host disease (GVHD) induced by intradermal injection of autoreactive T cells the epidermal structures spontaneously recovered from the destruction became resistant to the subsequent attempts to induce the cutaneous GVHD and that the resistance correlated well with a 30-fold increase in the number of Thy-1+ epidermal cells (Thy-1+EC). We show that the resistance to the cutaneous GVHD was never induced in athymic nude mice and adult thymectomy lethal radiation and bone marrow reconstitution (ATXBM) mice under the same conditions, indicating that the induction of the resistance is dependent on the presence of thymus. A great increase in the number of Thy-1+EC was similarly observed in the epidermis of the athymic nude and ATXBM mice that spontaneously recovered from the cutaneous GVHD and that remained susceptible to the induction of the cutaneous GVHD. However, the results with B10Thy-1.1----B6 radiation chimeras clearly demonstrate that the vast majority of the increased Thy-1+EC found in the "susceptible" epidermis of the ATXBM mice were of donor bone marrow origin and there was no increase in the number of host-derived Thy-1+EC, whereas in the "resistant" epidermis of the XBM mice both Thy-1+EC populations were equally increased. The overall results indicate that the expansion of Thy-1+EC that mature in the thymus is crucial to the induction of the resistance, although the migration of bone marrow-derived Thy-1+EC precursors to the epidermis occurs quite independently of the presence of thymus.

Animals↗
PubMed1990

Loss of epidermal integrity by T cell-mediated attack induces long-term local resistance to subsequent attack. I. Induction of resistance correlates with increases in Thy-1+ epidermal cell numbers.

The cutaneous graft-versus-host disease (GVHD) lesions induced by intradermal injection of cloned autoreactive T cells have been shown to subside rapidly and the epidermis returns to normal 2 wk after injection. Those mice that had spontaneously recovered from the cutaneous GVHD became resistant to subsequent attempts to induce the cutaneous GVHD by the T cells while maintaining their activity to mount delayed-type hypersensitivity (DTH) responses and to induce the enlargement of the popliteal lymph nodes (PLN). The resistance appeared to be restricted to the epidermal structures of the injection sites, suggesting the involvement of locally acting suppression mechanisms. This local resistance was not specific for the clonotype used for the induction of the resistance. A loss of the epidermal integrity by an attack of T cells capable of producing cutaneous GVHD was a prerequisite for the induction of the resistance. By up to at least 8 mo after injection of the T cells, no mice became susceptible to the cutaneous GVHD again, provided that the T cells were injected into the same footpad sites that had initially received the T cells. This resistance correlated well with the great increase (20-30-fold) in Thy-1+ EC number. The great increase in the number of Thy-1+ EC following destruction of epidermal structures may be important in protecting the epidermal integrity from an additional attack by T cells.

Animals↗
PubMed1990

Drug-induced, photosensitive, erythema multiforme-like eruption: possible role for cell adhesion molecules in a flare induced by Rhus dermatitis.

Drug-induced, photosensitive erythema multiforme has not been reported, although drugs and sunlight are listed among precipitating factors in erythema multiforme. We describe a case of a drug-induced erythema multiforme-like eruption in a photodistribution that was reproduced by clinical challenge with the drug and sunlight. On contact with Rhus verniciflua, the Japanese lacquer tree, the patient had a flare of the eruption, which was limited to the areas previously exposed to sun. Immunohistochemical studies suggested that the keratinocytes in the skin that retain teh photoactivated substances may facilitate epidermal invasion of lymphocytes by persistent expression of intercellular adhesion molecule-1.

Adult↗
PubMed1990

Both epidermal dendritic cell populations, Langerhans' cells and Thy 1+ dendritic cells are simultaneously stained by an Lyt-1 monoclonal antibody.

Both Langerhans' cells (LC) and Thy 1+ dendritic epidermal cells (DEC) are bone marrow-derived epidermal cells that are thought to play an important role in immune responses. Despite their several similarities, the surface phenotypes of both cells appear to be almost mutually exclusive. We found that an anti-Lyt-1.2 monoclonal antibody that recognizes solely an epitope on certain T cells can crossreact with a shared epitope on both cell types. The morphological details of LCs and Thy 1+ DECs stained by the anti-Lyt-1.2 MAb was superior to those stained by either anti-I-A or anti-Thy-1 MAb. The availability of this MAb enables us to simultaneously view both cell populations in the same sections.

Animals↗
PubMed1989

Fixed drug eruption. Expression of epidermal keratinocyte intercellular adhesion molecule-1 (ICAM-1).

The pathogenic mechanism of preferential localization to certain skin sites of fixed drug eruption lesions has remained unknown. Skin biopsy specimens were obtained from four patients with fixed drug eruptions at various time points after final exposure to the causative drug and were studied immunohistologically using monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1, and HLA-DR. The expression of ICAM-1 by keratinocytes was confined exactly to the involved epidermis. In contrast, the expression of HLA-DR by keratinocytes was observed not only in the involved epidermis but also in the uninvolved epidermis, although to a lesser extent. In general, the intensity of expression of ICAM-1 by keratinocytes correlated well with the degree of epidermal invasion of lymphocytes but not with the degree of dermal lymphocytic infiltration. Interestingly, in fixed drug eruption lesions, basal keratinocytes still showed intense reactivity for ICAM-1 6 to 10 days after final exposure to the causative drug, at which time the expression of HLA-DR was already down-modulated. Such a strong dissociation between the expression of ICAM-1 and HLA-DR on lesional keratinocytes was never observed at any time in the normal skin of control patients challenged with dinitrochlorobenzene. These results suggest that localized misregulated expression of ICAM-1 by the keratinocytes may be one factor that explains the preferential site-specificity characteristic of fixed drug eruptions.

Adult↗
PubMed1989

Only dull CD3+ thymocytes bind to thymic epithelial cells. The binding is elicited by both CD2/LFA-3 and LFA-1/ICAM-1 interactions.

In view of the necessity for thymocytes to interact with thymic epithelial cells to differentiate into mature T cells, this study analyzed the binding between human thymocytes, cultured thymic epithelial cells (CTEC) and the required adhesion molecules. Immediately after separation, thymic epithelial cells (TEC) readily expressed ICAM-1, which is one of the ligands of LFA-1 cell adhesion molecules. However, the ICAM-1 expression was gradually lost upon culture of TEC. IFN-gamma re-induced ICAM-1 on the CTEC, and the ability of CTEC to bind to thymocytes was also increased by IFN-gamma treatment. The increase in binding seemed to be caused by the LFA-1/ICAM-1 interaction, since it was inhibited by anti-ICAM-1 monoclonal antibody (mAb) and anti-LFA-1 mAb. This suggests that the LFA-1/ICAM-1 interaction is also involved in vivo with the binding of thymocytes to TEC, which have been shown to express ICAM-1. To better understand the nature of the cells involved in binding, thymocytes were sorted into CD3-, CD3dull+, and CD3bright+ subsets (which are supposed to represent the immature, intermediate and mature stages of differentiation, respectively), and were examined for their binding to IFN-gamma-treated CTEC. The result showed that only the CD3dull+ subset bound to CTEC. CD3-, CD3bright+ cells and peripheral blood T lymphocytes did not bind, but they were induced to bind by neuramidase treatment All these bindings were inhibited by anti-LFA-1 mAb and anti-CD2 mAb. These findings indicate that CD3dull+ cells can bind to TEC via CD2/LFA-3 and LFA-1/ICAM-1 interactions. Other cells seemed not to bind to TEC because of sialylation.

Antibodies, Monoclonal↗
PubMed1989

Interferon-gamma as adjuvant therapy for resistant warts.

A patient who for 26 years had common warts, which were resistant to various treatment modalities, was treated with a single intralesional injection of interferon-gamma after dinitrochlorobenzene immunotherapy, because immunologic studies indicated she had failed to respond to prior treatment modalities as a result of a functional impairment of her cellular immune response. Within 1 to 2 days, not only the wart injected with interferon-gamma, but also other warts, became erythematous and swollen, giving a lichen planus-like appearance. Without additional injections of interferon-gamma, all warts disappeared completely, leaving slight pigmentation. Interferon-gamma would be most effective when used with, rather than instead of, other immunotherapy.

Biopsy↗
PubMed1989

In vitro migration of L3T4+ cloned T cells to epidermis: possible role for keratinocyte-derived factors.

Three types of L3T4+ cloned T cells with different antigen specificities, auto-, allo-, and antigen-reactive, were characterized with respect to their migratory potential using an in vitro migration assay under agar gel. Autoreactive T cells, BB5, and alloreactive T cells, SK 1, both of which have been proved to be epidermotropic in vivo, showed specific directional migration to the epidermis, whereas no directional migration was seen with non-epidermotropic cloned T cells and freshly isolated lymph node T cells. Both BB5 and SK 1 cells were equally attracted to all the epidermal fragments tested regardless of their I-A antigens. The directional migration of BB5 cells to the epidermis was significantly inhibited by the co-cultivation with the epidermis, but not the dermis. Studies with cell lines, the conditioned media (CM), and recombinant interleukin (IL) 1, 2, and 3 revealed that BB5 cells were chemotactically attracted to a transformed keratinocyte cell line PAM212 and, to a lesser extent, to the CM from PAM212 and IL-2, but not to IL-1 and IL 3. These results suggest that epidermotropic T cells may be preferentially trapped in an area with a high concentration of keratinocyte-derived growth factors as well as IL-2.

Animals↗
PubMed1989

Differential expression of lymphocyte function-associated antigen 1 (LFA-1) on epidermotropic and non-epidermotropic T-cell clones.

Various T-cell surface molecules are involved in T-cell adhesion, which is an essential requirement for epidermotropic migration of T cells. Our previous studies demonstrated that certain T-cell clones can migrate into the epidermis upon their intradermal inoculation into the footpads of recipient mice with relevant antigens, while other T-cell clones, despite their identical antigen specificities and functions, are non-epidermotropic. We therefore tested whether the differences in epidermotropism of these T cells could reside in the different levels of expression of T-cell surface molecules such as CD3, CD4, CD2, and lymphocyte function associated antigen 1 (LFA 1). The results of flow cytometric analysis showed that LFA-1 was preferentially expressed on the surface of epidermotropic T-cell clones, while non-epidermotropic T-cell clones were negative or very weakly positive for LFA-1 with one exception. After exposure to phorbol ester, epidermotropic clones with high levels of LFA-1 did not show any further up-regulation of LFA-1. In contrast, under identical conditions, significant up-regulation of LFA-1 was observed on non-epidermotropic T cells with low levels of LFA-1. However, even after exposure to phorbol ester, these T cells remained non-epidermotropic. These results suggest that the presence of high levels of LFA-1 on T cells is absolutely necessary for their epidermotropic migration, but its up-regulation is neither necessary nor sufficient to trigger the epidermotropic migration. High levels of LFA-1, regardless of cell activation, may be required to mediate stable cell adhesions leading to epidermotropic migration.

Animals↗
PubMed1989

Psoriasis and lichen planus: coexistence in a single patient. Are both diseases mutually exclusive?

The coexistence of psoriasis and lichen planus has been rarely reported, although both diseases are relatively common and have some features in common. A rare case of simultaneous occurrence of both diseases is presented. Spontaneous improvement of psoriasis occurred during the development of lichen planus and a subsequent disappearance of the lichen planus was associated with an exacerbation of the psoriasis. The clinical courses of the two diseases may not be independent of each other, but be affected by common factors. Immunohistochemical studies with lesional skin suggested local production of interferon-gamma, which may in part explain the improvement of the psoriasis during the development of lichen planus. Based on these immunohistochemical findings, we discuss a putative role for these lymphokines in the pathogenesis of the two diseases.

Adult↗
PubMed1989

[Successful treatment of cheilitis granulomatosis with potent inhibitors of mediator release--possible involvement of mast cells in the pathogenesis].

We report two cases of patients with cheilitis granulomatosis treated successfully with tranilast and ketotifen, both of which are known to be potent inhibitors or mediator release from mast cells. In one patient, complete resolution of the lesion occurred after 1 year of therapy. In another patient, the lesion also showed consistent, if not complete, improvement during the course of therapy. Because of the mechanism of the action, these agents have been widely used as therapeutic modalities for mast-cell-related diseases. We therefore measured numbers of mast cells in the lesions of cheilitis granulomatosis, in comparison with those in mucous cyst and lichen planus. Light microscopy of toluidine-blue-stained sections showed that mast cells, particularly those with ongoing degranulation, increased in number in the reticular dermis of the lesions of cheilitis granulomatosis. These findings suggest that mediators released from mast cells may be critical for the granulomatous inflammation in cheilitis granulomatosis.

Adolescent↗
PubMed1988

Locally administered monoclonal antibodies to lymphocyte function-associated antigen 1 and to L3T4 prevent cutaneous graft-vs-host disease.

In vivo treatment with mAb directed against T cell surface molecules has been shown to prevent or reverse graft-vs-host disease (GVHD) and experimental autoimmune diseases, where T cells play a critical role. In this study we investigated the effects of in vivo administration of anti-I-A, anti-L3T4, and anti-lymphocyte function-associated Ag 1 (LFA-1) mAb on the development of murine cutaneous GVHD and delayed-type hypersensitivity responses evoked by local transfer of class II-MHC Ag-restricted, cloned autoreactive T cells. Prevention of cutaneous GVHD was achieved with local administration of either anti-L3T4 or anti-LFA-1 mAb, but not with anti-I-A mAb, while delayed-type hypersensitivity responses were inhibited by all the mAb. These results indicate that an I-A Ag-independent mechanism may be also operative in the development of the cutaneous GVHD, unlike the delayed-type hypersensitivity responses. Anti-LFA-1 mAb appeared to be more potent at inhibiting cutaneous GVHD rather than delayed-type hypersensitivity responses, whereas anti-L3T4 mAb inhibited equally both the responses. These results suggest that LFA-1 molecule may be involved in the epidermal invasion of T cells. Treatment with anti-LFA-1 mAb was found to be still, although less, effective at preventing cutaneous GVHD, even if the mAb was administered after the development of cutaneous GVHD.

Animals↗
PubMed1988

Role of Langerhans cells in epidermotropism of T cells.

Certain T lymphocytes display a specific affinity for the epidermis (epidermotropism). Recent studies have suggested that Ia+ Langerhans cells (LCs) are possible targets for the epidermotropism. A variety of self-Ia-reactive cloned T cells were tested for their ability to migrate into the epidermis following intradermal inoculation into the footpads of syngeneic mice. Clone BB5 was chosen as representative of the epidermotropic T cells. We investigated whether the depletion of Ia+ LCs from the epidermis by tape-stripping could alter the migration of BB5 cells into the epidermis. The epidermal invasion of BB5 cells was markedly impaired in those mice whose LCs were depleted by 95% after repetitive tape-stripping. Because production of epidermal-derived thymocyte activating factor (ETAF) by the epidermal cells was augmented after repetitive tape-stripping, the diminished migration of BB5 cells into tape-stripped epidermis did not result from a decrease in ETAF production which is thought to attract T cells chemotactically. These results suggest that Ia+ LCs may play an inductive role in the preferential migration of T cells into the epidermis.

Animals↗
PubMed1988

Immunopathologic study of lichenoid skin diseases: correlation between HLA-DR-positive keratinocytes or Langerhans cells and epidermotropic T cells.

Skin biopsy specimens from 24 patients with different lichenoid skin diseases that had been proved histologically were studied immunohistologically. Marked differences were noted in the number of OKT6+/S100+ Langerhans cells within the epidermis and dermis in the lesional skin between lichen planus (and its related disease) and lupus erythematosus; in the former these cells were increased in number; in the latter they were decreased in number compared with those in uninvolved perilesional skin. Human lymphocyte antigen (HLA)-DR expression on keratinocytes was observed not only in lichenoid skin diseases but also in control cases without epidermal involvement. In the two cases of systemic lupus erythematosus, the uninvolved perilesional skin also show weak and focal HLA-DR reactivity in the basal layer. HLA-DR+ keratinocytes could play an important role at least in the perpetuation of epidermal cell damage mediated by T cells.

Epidermis↗
PubMed1988

Lichenoid tissue reaction induced by local transfer of Ia-reactive T-cell clones. III. Role of Ia+ keratinocytes in the epidermotropic migration of the T cells.

The role of Ia+ keratinocytes in epidermotropism of T cells was analyzed by using self-IA specific autoreactive cloned T cells with epidermotropic nature (termed BB5) and those without it (termed C10). These T-cell clones were injected into the footpads of syngeneic nude mice whose keratinocytes had been induced to express Ia by the iv injection of normal mouse serum. Ia expression by keratinocytes was associated with the increased epidermal invasion of BB5 cells, but did not render C10 cells capable of migrating into the epidermis. The migration of the T cells to epidermis was also studied in vitro using a migration assay under agar. Ia expression by keratinocytes significantly enhanced the in vitro migration of BB5 cells to the epidermis, but had no effect on the migration of C10 cells and freshly isolated unstimulated lymphocytes. We surmise from these results that Ia+ keratinocytes may facilitate the epidermal invasion of the T cells with epidermotropic nature, but not those without it. However, the possibility certainly exists that the observed preferential migration of BB5 cells to Ia+ keratinocytes may be secondary to the alteration of other factors associated with the Ia expression. The injection of normal mouse serum was accompanied by an increase in the production of epidermal cell-derived thymocyte activating factor (ETAF) indicating that the increased ETAF production may have contributed to some of the observed preferential migration of BB5 cells.

Animals↗
PubMed1988

In vivo effects of interferon-gamma and anti-interferon-gamma antibody on the experimentally induced lichenoid tissue reaction.

We investigated the in vivo effect of recombinant interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) treatment of mice on the development of the delayed-type hypersensitivity (DTH) reaction and lichenoid tissue reaction (LTR) following the local injection of cloned autoreactive T cells. Both the DTH reaction and the LTR were significantly enhanced by pretreatment with IFN-gamma, but not with TNF-alpha. Induction of class II MHC antigens on keratinocytes was not essential for the enhancement by IFN-gamma. Administration of anti-IFN-gamma antibody reduced the DTH reaction and LTR, although complete inhibition was not observed with our treatment regimen. The ability of IFN-gamma to increase the number of the cloned T cells invading the epidermis in vivo, is in keeping with our previous observation that IFN-gamma treatment of cultured keratinocytes markedly increased the adherence reaction between T cells and keratinocytes in vitro.

Animals↗