Experimental Studies On The Phenotype And The Role Of CD8~+T Cells In Psoriasis

Psoriasis is a common chronic inflammatory skin disease. Genetic factors play an important role in the process of this disease. The etiology and pathogenesis of psoriasis is still unclear so that it is lack of satisfactory therapies. Psoriasis is easily recurrent and hard to cure, seriously affects the patient’s quality of life. Recently, studies show that autoimmune disorder and aberrant biological behavior of keratinocytes play a certain role in the pathogenesis of psoriasis. In addition, abnormal activation of T cells is believed to be crucial in the pathogenesis of psoriasis. Objectives:To observe the subgroups and proportion of CD8+ T cells in the lesions and peripheral blood of patients with psoriasis, and investigate the effect of different subgroups of CD8+ T cells on pathogenesis of psoriasis. Methods:We collected 10 lesions of psoriatic patients, 8 lesions of patients with lichen planus, and 10 normal skins from healthy volunteers. We performed immunohistochemistry and immunofluorescence assay to observe the distribution of CD8α, CD8β, granzyme B, perforin, and CD107 a. In addtion, we collected the peripheral blood samples from 40 psoriatic patients, 20 patients with lichen planus and 40 healthy volunteers to detect the proportion of CD8α+α+ T cells and CD8α+β+ T cells. Moreover, we studied the expressions of IFN-γ, TNF-α, Granzyme B and Perforin in different subgroups of CD8α+α+ T cells and CD8α+β+ T cells derived from psoriatic patients, patients with lichen planus and healthy volunteers. At last, we used t test to analyze the data of experimental groups and control groups by Graphpad Prism. Results:Fristly, we observed that CD8α+α+ T cells were mainly infiltrated in psoriatic lesions, rather than CD8α+β+ T cells. While we did not found CD8α and CD8β expressed in healthy skin. Secondly, flow cytometry assay show that the proportion of CD8α+α+ T cells in peripheral blood of healthy person is 12.26% ± 2.35%, the proportion of CD8α+β+ T cells is 82.74% ± 2.35%, the proportion of CD8α+α+ T cells in peripheral blood of patients with psoriasis is 29.48% ± 3.20% and the proportion of CD8α+β+ T cells is 67.10% ± 3.77%. Compared with normal control groups, the proportion of CD8α+α+ T cells in peripheral blood of patients with psoriasis is obviously incerased(t = 3.08,P < 0.01), while the proportion of CD8α+β+ T cells in peripheral blood of patients with psoriasis is obviously decreased(t = 3.52,P < 0.01). In addtion, IFN-γ and TNF-α secreted by CD8α+α+ T cells in peripheral blood of 10 patients with psoriasis is 13.44% ± 3.26 and 34.03%± 6.09%, and secreted by CD8α+β+ T cells is 26.25% ± 4.25 and 23.56% ± 4.72%;The IFN-γ and TNF-α secreted by CD8α+α+ T cells in peripheral blood of 8 healthy person is 13.44% ± 3.26 and 34.03%± 6.09%, and secreted by CD8α+β+ T cells is 5.69% ± 1.40 and 13.45% ± 2.25%. In normal control groups, the IFN-γ and TNF-α secreted by CD8α+α+ T cells is much higher than CD8α+β+ T cells(t= 2.19&3.1,P < 0.05&0.01). Meanwhile in peripheral blood of patients with psoriasis, we found that IFN-γ and TNF-α secreted by CD8α+α+ T cells is much higher than CD8α+β+ T cells(t=2.41&3.74,P< 0.05&0.01). Moreover, we found co-localization of CD8α and Granzyme B, CD8α and Perforin in psoriatic lesions and patients with lichen planus’ lesions, but not detected in normal skin. And in peripheral blood of patients with psoriasis, patients with lichen planus and healthy person, the expression of Granzyme B in CD8α+α+ T cells were much higher than CD8α+β+ T cells(t=3.57, 3.16 and 2.77; P < 0.01, 0.01 and 0.05). However, in peripheral blood of patients with psoriasis, the expression of Perforin in CD8α+β+ T cells was significantly higher than the normal control group(t = 2.17, P < 0.05). But the expression of perforin in CD8α+α+ T cells had no significant difference with the CD8α+β+ T cells in patients with psoriasis and lichen planus of peripheral blood. At last, we find that in dermis of patients with lichen planus, there were many CD107 a, but only a few of them were co-expression with CD8α; but not found in patients with psoriatic skin lesions and healthy skin. Conclusions:Our study indicated that CD8+ T cells plays an important role in pathogenesis of psoriasis. We found that the CD8α+α+ T cells may be the key CD8+ T subset involved in the pathogenesis of psoriasis. These CD8α+α+ T cells contribute to psoriasis by secreting IFN-γ and TNF-α. Interestingly, we found that the CD8α+α+ T cells secrete Granzyme B and Perforin in psoriatic lesions, but we did not observed killing phenomenon at the tissue level. The mechanism by which CD8α+α+ T cells contribute to psoriasis need to be further investigate.