痤疮丙酸杆菌.ppt

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1、Propionibacterium acnes-Reactive T Helper-1 Cells in the Skin of Patients with Acne Vulgaris存在于寻常痤疮患者皮肤中的痤疮丙酸杆菌T助细胞1To the Editor:Acne vulgaris is the commonest skin disorder to affect humans,characterized by both noninfammatory(comedones)and inflammatory lesions(papules,pustules,and nodulocystic le

2、sions).It is a disease of the pilosebaceous follicle with comedones resulting from thehypercornification of the keratinocytes of the duct wall and usually preceding inflammatory lesions(Cunliffeetal,2000).寻常痤疮是最普通的能影响人体健康的皮肤紊乱疾病，既有非发炎性（如粉刺）又有发炎性（如丘疹、脓包、结囊肿损害）损害特点，这是一种毛皮脂腺囊疾病，输送管壁的角蛋白超角质化或上面提到的发炎性损害导

3、致了粉刺的形成（Cunliffe et al，2000）Of particular interest in the pathophysiology of inflammatory acne is the role of the normal skin commensal bacterium Propionibacterium acnes.Although not a requirement for comedogenesis,a number of observations have suggested that P.acnes is implicated in the pathogenesi

4、s of inflammatory acne.至于病理生理学上的发炎性损害，正常皮肤共生的细菌丙酸杆菌粉刺起着特殊作用，尽管并不需要分生孢子，但是通过观察发现丙酸杆菌粉刺和感染性损害的发病机制有关系 The density of P.acnes increases markedly during puberty coinciding with the onset of the disease(Leyden et al,1975).P.acnes is rarely found in animal skin and acne is not seen in animals(Webster et a

5、l,1981;Kearney et al,1982).Treatments that reduce P.acnes numbers lead to clinical improvement of acne(Thiboutot,1997)and,finally,the emergence of antibiotic-resistant P.acnes strains are linked to the failure of antibiotic treatment(Eady et al,1989).该病始于青春期，此间丙酸杆菌分析的数量显著增加，很少在动物皮肤发现丙酸杆菌痤疮，在动物体内也无发现

6、痤疮，试图通过临床试验减少痤疮丙酸杆菌数量，抗生素疗法因为产生了抵抗抗生素的菌株而失败（Eady et al，1989），The immunostimulatory activity of P.acnes and resulting prototypic T helper 1 immune response has been widely studied in animal models(Matsui et al,1997;Okazaki et al,2001);however,the specificity and cytokine profiles of lesional T cells

7、from skin of acne patients have not been investigated previously已经利用动物模型对痤疮丙酸杆菌引起的免疫活动和由原T助细胞引发的免疫应答进行了广泛的研究，然而还没有对痤疮病人皮肤受损害的T细胞原型及细胞因子原型的研究，Here we describe the generation of T cell lines (TCL)from inflamed acne lesions,and,their proliferative and cytokine responses to P.acnes antigens.Approval was

8、 granted for this research project by the Hammer-smith Queen Charlottes&Chelsea and Actin Hospitals Research Ethics Committee.Full consent was granted by subjects这里我们将描述TCL的产生、增值以及细胞因子对痤疮丙酸杆菌抗原的免疫反应。Fourteen TCL were generated from early papular inflammatory acne lesions of 16 untreated patients,sta

9、ined for CD4,CD8,and T cell receptor expression and tested in proliferation assays with P.acnes and control antigens.To determine their cytokine profile,TCL were stimulated with phorbal 12-myristate 13-acetate (PMA)plus ionomycin or P.acnes extract and stained intracellularly for interferon(IFN)-,in

10、terleukin(IL)-4,IL-5,and IL-10 using fow cytometry.Results were compared with eight corresponding TCL generated in the same way from lesional skin of 11 psoriatic patients.十四TCL取自于16位未经处理的患早期丘疹感染损害的病人，CD4、CD8染色，T细胞受体表达，增值实验检测P.粉刺与控制抗原（图1），为了确定细胞因子原型，以流式细胞术刺激TCL，用PMA加离子霉素或P.粉刺提取物以及细胞内的染色干扰素、白细胞介素（IL）

11、4、IL5、IL10，结果与采用相同方式从11位牛皮癣患者取出的8个TCL分析结果相比较。Acne TCL consisted of T cell receptor +T cells(96.474%)with a predominance of CD4(9277.5%)phenotype,whereas psoriatic TCL contained a higher percentage of CD8+T cells(24.8+21.4%;p0.05).This is in agreement with an earlier immunohistochemical study that de

12、monstrated perivascular and periductal infiltrates of CD4+T cells in early acne skin lesions(Layton et al,1998);痤疮TCl的T细胞受体+T细胞（96.4+-4%），含有较为显著的CD4+（92+7.5），然而牛皮癣TCL含有更多的CD8+T细胞，这与先前的免疫组化研究结果相一致，表明早期粉刺皮肤病灶血管周围和导管周围含有CD4+T细胞 however,the stimulus for T cell infiltration into acne lesions remains to b

13、e determined.The initial T cell infiltrate may represent a specific cell-mediated immune response to P.acnes antigens within the ductal lumen.In support of this hypothesis,this study has shown that all acne TCL proliferated to P.acnes extract(optimal concentration 1:100)with a wide range of responses (mean 642074545 cpm).但是导致导致这一结果的刺激还未被确定，初始T细胞浸润可能代表着在导管腔内发生的对P.粉刺产生的特异性的细胞介导免疫反应，该实验表明P.粉刺浸提物（最是浓度1:100）能使所有的粉刺TCL大范围增殖（平均6420+_4545cpm）