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.
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.
Clinic for Rheumatology and Clinical Immunology/Allergology, University of Bern, Bern, Switzerland. nyawalker@RICS.bwh.harvard.edu
N
N
Yawalkar
R E
RE
Hunger
C
C
Buri
S
S
Schmid
F
F
Egli
C U
CU
Brand
C
C
Mueller
W J
WJ
Pichler
L R
LR
Braathen
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D012313:RNA / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D012313:RNA; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases