Baker Barbara S, Ovigne Jean-Marc, Fischetti Vincent A, Powles Anne, Fry Lionel
Department of Dermatology, Faculty of Medicine, Imperial College of Science, Technology & Medicine, London, United Kingdom.
J Clin Immunol. 2003 Sep;23(5):407-14. doi: 10.1023/a:1025377702283.
We have recently described a group A streptococcal (GAS)-reactive Th-1 subset specifically present in skin lesions of chronic plaque psoriasis. To investigate MHC presentation of GAS cell wall proteins, dermal T cell lines (TCL) cultured from the lesional skin of 39 HLA-typed psoriasis patients were stimulated with a cell wall extract, stained for intracellular IFN-gamma expression, and analyzed by flow cytometry. TCL from a further seven psoriasis patients were also tested with S. mutans extract. Eight TCL were tested in the presence of anti-Class II antibodies or allogeneic antigen-presenting cells. The dermal T cell IFN-gamma responses to the cell wall extract, which ranged from < 1 to 28%, were significantly higher than that to S. mutans extract (p = 0.0052) and were self-HLA-DR allele restricted. A significantly decreased response was observed in TCL from DR15+ (n = 13) versus DR15- (n = 26) patients (p = 0.0377). In addition, DR15+ patients had a later age of onset of disease and a decreased history of sore throats. In contrast, TCL from HLA-DR7+ (n = 23) patients responded similarly to those from individuals lacking the DR7 allele. However, DR7+ patients who coexpressed the MHC Class I antigen, Cw6 (n = 14) had a significantly higher IFN-gamma response than Cw6-, DR7+ patients (n = 7; p = 0.0288) whose responses were also significantly lower than those of patients expressing non-DR7 alleles (n = 16; p = 0.0302). This study has shown that HLA-DR15 expression is associated with a reduced dermal Th-1 response to GAS cell wall proteins in patients with psoriasis. It is proposed that HLA-DR allelic variation may contribute to disease phenotype via effects on the immune response to group A streptococci.
我们最近描述了一组特异性存在于慢性斑块状银屑病皮肤病变中的A组链球菌（GAS）反应性Th-1亚群。为了研究GAS细胞壁蛋白的MHC呈递情况，用细胞壁提取物刺激从39例HLA分型的银屑病患者皮损皮肤培养的真皮T细胞系（TCL），对细胞内IFN-γ表达进行染色，并通过流式细胞术进行分析。另外7例银屑病患者的TCL也用变形链球菌提取物进行检测。8个TCL在抗II类抗体或同种异体抗原呈递细胞存在的情况下进行检测。真皮T细胞对细胞壁提取物的IFN-γ反应范围为<1%至28%，显著高于对变形链球菌提取物的反应（p = 0.0052），且受自身HLA-DR等位基因限制。与DR15-（n = 26）患者相比，DR15+（n = 13）患者的TCL反应显著降低（p = 0.0377）。此外，DR15+患者的疾病发病年龄较晚，咽痛病史较少。相比之下，HLA-DR7+（n = 23）患者的TCL反应与缺乏DR7等位基因个体的TCL反应相似。然而，共表达MHC I类抗原Cw6的DR7+患者（n = 14）的IFN-γ反应明显高于Cw6-、DR7+患者（n = 7；p = 0.0288），后者的反应也明显低于表达非DR7等位基因的患者（n = 16；p = 0.0302）。这项研究表明，HLA-DR15表达与银屑病患者真皮Th-1对GAS细胞壁蛋白的反应降低有关。有人提出，HLA-DR等位基因变异可能通过影响对A组链球菌的免疫反应而导致疾病表型。
