A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B - PubMed (original) (raw)

Comparative Study

A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B

N Yawalkar et al. Am J Pathol. 2001 Mar.

Abstract

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.

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Figures

Figure 1.

Expression of perforin and granzyme B is strongly enhanced in contact dermatitis. In situ hybridizations (A) and immunohistochemistry (B) of cryostat sections form normal skin, lesional contact dermatitis and psoriatic skin are shown. Perforin (a and g) and granzyme B (d and j) gene expression and immunoreactivity was barely detectable in normal skin. A marked enhancement of perforin (b and h) and granzyme B (e and k) expression was observed in the mononuclear cell infiltrate in contact dermatitis. Perforin (c and i) and granzyme B (f and l) expression was found in a few cells in psoriasis. Original magnification, ×250.

Figure 2.

Quantification of perforin- and granzyme B-positive cells in normal skin (n = 6), contact dermatitis (n = 8), and psoriatic skin lesions (n = 6). Mean values ± SEM.

Figure 3.

Perforin (a) and granzyme B (b) immunoreactivity was found particularly at sites of spongiosis or near spongiotic vesicles in the epidermis. Positively stained lymphocytic cells were observed in close relationship with damaged keratinocytes (arrow). Note that positive immunostaining was also observed on keratinocytes (arrowhead) next to lymphocytic cells expressing cytotoxic proteins (inset). Original magnification, ×400.

Figure 4.

Perforin and granzyme B are expressed in CD4+ and CD8+ cells. Double immunostaining was performed as described in Materials and Methods. Representative stainings of perforin and granzyme B with different chromogens are shown. In the upper panel CD4+ (a) and CD8+ (b) cells were determined with diaminobenzidine (brown), perforin with new fuchsin-naphtol (red). In the lower panel CD4+ (c) and CD8+ (d) cells were determined with TMB (green), granzyme B with Fast Red (red). Arrows indicate double-positive cells. Original magnification, ×1000.

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A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B - PubMed (original) (raw)