The effect of anti-CD4 monoclonal antibody treatment on immunopathological changes in psoriatic skin.
Recent clinical studies which showed the therapeutic effect of cyclosporin A and of anti-CD4 MoAb emphasized the role of activated CD4+ T cells infiltrating the lesional skin in the pathogenesis of psoriasis. The aim of the present study was to analyze the mode of action of anti-CD4 MoAb in 3 psoriatic patients who experienced an anti-CD4 MoAb-induced clinical improvement maximal 3-4 weeks after the onset of an 8-day therapy. We evaluated the effect of anti-CD4 MoAb treatment on the phenotype of resident and passenger inflammatory skin cells in lesional skin samples. We observed a gradual improvement of 3 out of 4 histopathologic features including parakeratosis, papillomatosis and acanthosis. In the dermis there was no modification in the density of the dermal mononuclear cell infiltrate, which consisted mainly of CD3+, CD45RO+, TCR alpha beta+, CD11a+, HLA-DR+T cells with a CD4/CD8 cell ratio of 1.5/1. Therefore as previously observed for peripheral blood mononuclear cells, the number of CD4+ T cells infiltrating the dermis remained unaffected by the treatment. In contrast, CD4 MoAb treatment was associated with drastic changes in the epidermis. These included a decrease in both CD4+ and CD8+ epidermal T cell infiltrate, diminished numbers of ICAM-1+ and HLA-DR+ keratinocytes and restored numbers of CD1a+ epidermal Langerhans cells. We conclude from this study that clinical improvement of psoriasis by anti-CD4 MoAb therapy paralleled: (1) a decrease in epidermal T cells, and (2) a down-regulation of keratinocyte activation markers (ICAM-1 and HLA-DR). These results suggest that the observed changes are secondary to down-regulation of inflammatory cytokine production by T cells in situ.
Rizova
H
H
Clinique Dermatologique, Hopital E. Herriot, Lyon, France.
Nicolas
J F
JF
Morel
P
P
Kanitakis
J
J
Demidem
A
A
Revillard
J P
JP
Wijdenes
J
J
Thivolet
J
J
Schmitt
D
D
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D015603:Keratinocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000473:pathology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens