Selective Persistence of Dermal CD8+ T Cells in Lesional Plaque Psoriasis after Clobetasol‐17 Propionate Treatment

Abstract

In psoriasis, T-cell infiltration and epidermal hyperproliferation are key phenomena which are closely related. Our aim was to investigate the dynamics among T-cell subsets in relation to epidermal proliferation and clinical severity in psoriasis during treatment with an ultra-potent corticosteroid. Seven psoriasis patients were treated twice daily for 14 days with clobetasol-17 propionate ointment. Punch biopsies were taken at day 0, 3, 7 and 14. Epidermal proliferation marker Ki-67 and CD4+, CD8+, CD45RO+, CD2+ T cells were quantified by immunohistochemical techniques and image analysis. The clinical score declined significantly (60%; p<0.01) and a 47% reduction of Ki-67+ nuclei was observed after only 3 days (p<0.01). In the epidermis all investigated T-cell subsets were significantly reduced at day 14 (p<0.05). In the dermis, treatment resulted in a significant decrease of CD4+, CD45RO+ and CD2+ T cells, but dermal CD8+ T cells persisted. In psoriasis, reduction of clinical severity and epidermal proliferation during the early phase of topical corticosteroid therapy cannot primarily be the result of decreased T-cell subsets. Furthermore, selective persistence of dermal CD8+ T cells was observed, which might be associated with disease relapse.

Influence of phototherapy in psoriasis on ki-67 antigen expression: a preliminary study

“…Three days following the application of 0.05% clobetasol propionate in patients with moderate and severe psoriasis the number of Ki-67 positive nuclei in the epidermis dropped by 47%. After 2 weeks the drop was 87% [23]. Van Duijnhoven et al confirmed in their study that the treatment with betamethasone valerate (0.1% cream) for two weeks contributed to a significant decrease in the Ki-67 expression index in the epidermis.…”

“…In a study conducted by Bovenschen et al on atopic dermatitis and lichen planus the number of epidermal cells in which nuclei demonstrated the presence of the Ki-67 antigen was half that in psoriasis, i.e. the percentages of the epidermal cells in these two disorders were 54% and 52% respectively [23]. Soini et al observed a higher percentage of Ki-67 positive cells in chronic dermatitis and lichen planus in comparison with psoriasis.…”

Induced keratinocyte hyper-proliferation in α2β1 integrin transgenic mice results in systemic immune cell activation

“…CD8 + T cells cannot do this job and therefore CD4 + T cells are considered essential [23,24]. Still, there is other evidence supporting a major role for CD8 + T cells [25][26][27] as well as cells from the innate immune system such as macrophages and dendritic cells (DC) [28][29][30][31]. The fact that psoriasis has not been shown to be linked to any specific MHC II allele but in contrast, show strong genetic linkage to the MHC I, argues for a major role of CD8 + T cells [32].…”

Identification of Lesional CD4+ CD25+ Foxp3+ Regulatory T Cells in Psoriasis

“…The depletion or malfunctioning of T reg , such as in psoriasis, is associated with a massive expansion of the CD8+ T cell population [36]. The (epidermal) CD8+ T cell population, in turn, has been demonstrated to play a major role in the pathogenesis of psoriasis [2, 5, 7, 37, 38]. Whether T reg in psoriatic plaques are naturally occurring or adaptive cells, both of which express their suppressive function in different ways, remains to be elucidated.…”