http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808928/
In psoriasis, the importance of effector/memory T cells is now generally recognized [ 25 ], but it remains to be elucidated where the effector T cells are activated. It has been observed that CLA + T cells, especially the CD8 + subpopulation, resides within the tonsils in higher frequency than in blood or abdominal lymph nodes and selective homing of CLA + T cells into the tonsils is unlikely as endothelial expression of E-selectin is very low in the tonsils [Thorleifsdottir et al . unpublished observation]. Furthermore, high frequency of clinical remission of psoriasis has been reported after tonsillectomy [ 26 , 27 ]. It is therefore tempting to argue that the priming of the effector and memory T cells that cause psoriasis, especially the guttate variant, may at least to some extent take place in the tonsils, which interestingly is the only mucosal lymphoid organ lined with stratified epithelium [ 28 ].
PSORIASIS IS A T CELL-MEDIATED DISEASE
Although a case report in 1979 suggested that cyclosporin A could clear psoriasis [ 29 ], this disease was generally considered to be a primary disorder of keratinocytes in the early eighties. A direct role of T cells in the pathogenesis of psoriasis was first suggested in 1983 [ 30 ], and it was independently demonstrated that the eruption of psoriatic skin lesions coincided with epidermal influx of dendritic cells (DCs) and T cells [ 31 ] and that resolution of psoriatic lesions during phototherapy was preceded by depletion of T cells, especially from the epidermis [ 32 ]. The efficacy of cyclosporin A in psoriasis was subsequently confirmed in two independent studies [ 33 , 34 ] and trials with anti-CD4 monoclonal antibodies [ 35 ] and an interleukin-2-toxin conjugate [ 36 ] further supported that psoriasis is a T cell-mediated disease. These T cell-specific treatments resulted in the normalization of the keratinocyte proliferation and epidermal thickening. The key role of T cells in psoriasis was conclusively demonstrated in 1996 when psoriatic lesions were induced by injecting autologous T cells into uninvolved psoriatic skin transplanted to SCID mice [ 37 ]. It was further shown in this model that psoriatic lesions could be induced by injecting purified CD4+ T cells into uninvolved psoriatic skin but no changes were seen when purified CD8+ T cells were injected [ 38 ]. Although CD4+ T cells therefore seem to be essential for initiating psoriatic lesions, CD8+ T cells may also have an important role in the pathogenic process as uninvolved psoriatic epidermis contains an increased number of CD8+ T cells that may be able to proliferate locally with the help of IL-7 and IL-15 [ 39 , 40 ], cytokines that are produced by keratinocytes [ 41 ].
