Recruitment of CD8+ T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis
Recruitment of CD8+ T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis
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DOI：
10.1111/j.1365-3024.2009.01125.x
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发表时间：
2009-08-01
影响因子：
2.2
通讯作者：
Dutra, W. O.
中科院分区：
文献类型：
--
作者：
Faria, D. R.;Souza, P. E. A.;Dutra, W. O.
人类感染巴西利什曼原虫会导致皮肤利什曼病(CL)，其特征是皮肤出现从非溃烂到溃烂的皮损。我们的目标是通过比较早期(E-CL)和晚期(L-CL)CL患者皮损中的细胞成分、细胞因子和颗粒酶的表达，来表征与这一进展相关的免疫动力学。组织病理学分析显示，与E-CL组相比，L-CL组有更多的炎性细胞浸润。虽然E-CL和L-CL的皮损以单核为主，但E-CL患者的中性粒细胞和嗜酸性粒细胞计数高于L-CL。L-CL的CD_4(+)和CD_(68)细胞的百分率略高于E-CL，而CD_8(+)细胞的百分率L-CL是E-CL的5倍。此外，L-CL的CD8(+)T细胞表达的颗粒酶A水平明显高于E-CL。有趣的是，在L-CL中，颗粒酶A的表达与炎性浸润物的强度呈正相关，而在E-CL中则不相关。L-CL组干扰素-γ(+)和IL-10(+)细胞的百分率高于E-CL组，CD_4(+)T细胞和CD_(68)单核细胞分别是这两种细胞因子的主要来源。这些结果提示CD8(+)颗粒酶A(+)T细胞的募集参与了CL的病变进展。
P>Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from nonulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4(+) and of CD68(+) cells were slightly higher in L-CL, a fivefold increase of CD8(+) cells was observed in L-CL, as compared to E-CL. Moreover, CD8(+) T-cells from L-CL expressed significantly higher levels of granzyme A than E-CL. Interestingly, granzyme A expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-gamma(+) and IL-10(+) cells were higher in L-CL as compared to E-CL, with CD4(+) T-cells and CD68(+) monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8(+) granzyme A(+) T cells is involved in lesion progression in human CL.