Six patients received 12 weekly doses of LFA3TIP, a fully human LFA-3/IgG1 fusion protein. 6 mm biopsies were performed at baseline and weeks 7 and 13 (1 week after ®nal dose). Biopsies were snap frozen and analyzed for immunohistochemical markers (CD3, CD4, CD8, and CD2), Ki67, keratin 16, and epidermal thickness. Pan-T cell staining with CD3 demonstrated a decrease in the numbers of epidermal T cells present in 4/6 patients while dermal T cells decreased in 3/6. Staining for CD2 was similar

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... the CD3 data and results were also consistent with staining for CD4 and CD8. CD4 staining was primarily in the dermis and was only slightly decreased in 3/6 samples at week 13, while CD8 staining was primarily in the epidermis and showed signi®cant decreases in 4/6 patients by week 7. Notably, the epidermal effects at the week 7 biopsy antedated the dermal changes. Dermal changes including reduction in Ki67 staining (5/6 samples) and a diminution of keratin 16 expression (4/6 patients) were of lesser magnitude and were evident between week 7 and 13. These data suggest a differential sensitivity between dermal CD4+ T cells and epidermal CD8+ T cells to LFA3TIP. By having a signi®cantly greater effect on epidermal CD8+, most of which are likely to be CD45RO+, LFA3TIP may preferentially reduce the activated cells directly interacting with keratinocytes in psoriasis, while relatively sparing CD4+. Moreover, since changes in epidermal T cells preceded other immunohistochemical changes (e.g. Ki-67 and keratin 16), the data provide in vivo proof of the proximal nature of CD8+ T cells in the psoriatic lesion. Altering CD8+ T cells speci®cally with relative sparing of dermal CD4+ T cells appears to reduce the activity of psoriasis. Biologics (e.g. LFA3TIP) capable of targeting speci®c lymphocyte subsets can give important insights into the pathogenesis of T cell-mediated autoimmune disorders.