Masaji Nagashima

Role of Langerhans cells in epidermotropism of T cells

SummaryCertain 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.

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.

The lichenoid tissue reaction. A new concept of pathogenesis.

T lichenoid tissue reaction (LTR) is characterized by epidermal basal cell damage that is intimately associated with a massive infiltration of mononuclear cells in the upper dermis.^ Although it has been suggested for a long time that the epidermal basal cell damage seen In the LTR is the result of a local cellmediated immune response,^ the mechanism or mechanisms by which epidermal cells are damaged remain unknown. A recent explosion of information about lymphokines and cytokines, secreted by lymphocytes and nonlymphoid cells respectively, has led us to propose a new concept of the pathogenesis of the LTR, In this review, we will focus on how such information may afford new insight into the pathogenesis of the LTR. For a survey of other aspects of the LTR, the reader is also referred to an excellent previous review by Weedon.^

Prurigo pigmentosa--clinical observations of our 14 cases.

Clinical observations of fourteen Japanese patients with prurigo pigmentosa, a peculiar pruritic pigmented dermatosis, were reported. Clinically the dermatosis is characterized by the sudden appearance of reddish papules accompanied by severe pruritus. Gross reticular pigmentation occurred after the disappearance of the papules. Histopathological findings of the papular lesions are non‐specific, although they show lichenoid tissue reactions. The dermatosis shows some preference for females, particularly in adolescence. Sites of predilection are the back, the nucha, the clavicular regions and the chest. Although the cause of the disease still remains unknown, it is speculated that some unknown environmental contaminant in todays Japan may play a role in the development of this dermatosis.

Granulomatous cheilitis and Crohn's disease

A case of granulomatous cheilitis is reported in whom investigations showed intestinal involvement compatible with Crohns disease, although the patient had no gastrointestinal symptoms.

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

We investigated the in vivo effect of recombinant interferon‐γ (IFN‐γ) and tumour necrosis factor α (TNF‐α) 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 pre‐treatment with IFN‐γ, but not with TNF‐ã. Induction of class II MHC antigens on keratinocytes was not essential for the enhancement by IFN‐γ. Administration of anti‐IFN‐γ antibody reduced the DTH reaction and LTR, although complete inhibition was not observed with our treatment regimen. The ability of IFN‐γ to increase the number of the cloned T cells invading the epidermis in vivo, is in keeping with our previous observation that IFN‐γ treatment of cultured keratinocytes markedly increased the adherence reaction between T cells and keratinocytes in vitro.

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.

Erythema nodosum, Lichen planus and Lichen nitidus in Crohn’s Disease: Report of a Case and Analysis of T Cell Receptor V Gene Expression in the Cutaneous and Intestinal Lesions

A wide variety of cutaneous manifestations have been described in association with Crohns disease (CD). We describe a patient with a 2-year history of CD who developed both lichen planus (LP) and lichen nitidus (LN) in addition to erythema nodosum (EN) lesions. The clinical course of EN reflected the activity of the bowel disease, whereas LP and LN appeared to persist independently of the ongoing disease activity. Immunohistochemical studies of the infiltrates in these cutaneous and intestinal lesions showed that the majority of the infiltrates were T cells expressing T cell receptor (TCR)-alpha beta. Analyses of TCR V gene expression in these infiltrating T cells demonstrated a different pattern of V beta expression that provides an explanation for the difference in the clinical courses of these lesions. LP and LN lesions are likely to be mediated by T cells with antigen specificity distinct from those that cause EN and intestinal lesions.

Induction of cutaneous graft-versus-host disease by allo- or self-Ia-reactive helper T cells in mice.

Recent evidence suggests that Ia+ Langerhans cells may be a primary target for destruction in cutaneous graft-versus-host disease (GVHD). Although it is generally accepted that T lymphocytes with helper/inducer phenotype are essential, the identity of the effector cells is still controversial. We therefore investigated whether a variety of la-reactive cloned helper T cells with different cross-reactivities and functions in vitro can induce cutaneous GVHD following intradermal inoculation into the footpad of the appropriate recipients, whose la antigens are able to stimulate the T cells to proliferate in vitro. All cloned T cells tested caused significant footpad swelling in their appropriate recipients with a course typical for local cutaneous delayed-type hypersensitivity (DTH) reactions. Two of these cloned T cells, SK 1 and BBS, induced local histologic changes consistent with grades 2–3 of cutaneous GVHD in the appropriate allogeneic or syngeneic recipients at 48–72 hr after their intradermal inoculation. Immunohistochemical studies using monoclonal antibodies demonstrated that not only injected cloned T cells but also Lyt-1+ cells derived from the recipient migrate into the epidermis and are responsible for the destruction seen in cutaneous GVHD. In epidermis in which cutaneous GVHD had been induced, expression of Ia by keratinocytes and the damage of Ia+LC were observed. These results suggest that Ia+LC and Ia+ keratinocytes may play an important role in the infiltration of la-reactive T cells responsible for cutaneous GVHD.

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.