Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
J Clin Immunol. 2010 Mar;30(2):272-9. doi: 10.1007/s10875-009-9361-1. Epub 2010 Jan 23.
Human immunodeficiency virus (HIV)-infected individuals have CD8(+) cytotoxic T lymphocytes (CTL) that kill activated uninfected T lymphocytes. These CTL are independent of class Ia human histocompatibility-linked leukocyte antigens (HLA-Ia).
To further characterize these CTL, we investigated their possible restriction to non-classical class Ib HLA-E molecules and their expression of natural killer cell receptors (NKR) that are often affected in HIV infection.
We found no role for HLA-E in CTL-mediated killing of activated uninfected T lymphocytes. The non-HLA-restricted CTL did not express NKG2A, an inhibitory NKR that binds HLA-E, nor CD56, a prominent marker on previously described non-HLA-restricted CTL.
This NKG2A(-)CD56(-) phenotype of HLA-unrestricted CTL that kill uninfected activated T lymphocytes matches generalized changes on CD8(+) T lymphocytes that occur in progressive HIV infection, suggesting these phenotypic changes may reflect pathogenic evolution of the CD8(+) T cell repertoire. These CTL represent a unique phenotypic and functional subset with potential relevance to HIV pathogenesis.
感染人类免疫缺陷病毒 (HIV) 的个体具有杀伤激活的未感染 T 淋巴细胞的 CD8(+)细胞毒性 T 淋巴细胞 (CTL)。这些 CTL 不依赖于经典的 I 类人类组织相容性白细胞抗原 (HLA-Ia)。
为了进一步描述这些 CTL，我们研究了它们可能对非经典 I 类 HLA-E 分子的限制及其表达在 HIV 感染中经常受到影响的自然杀伤细胞受体 (NKR)。
我们没有发现 HLA-E 在 CTL 介导的杀伤激活的未感染 T 淋巴细胞中的作用。非 HLA 限制的 CTL 不表达 NKG2A，NKG2A 是一种结合 HLA-E 的抑制性 NKR，也不表达 CD56，CD56 是先前描述的非 HLA 限制的 CTL 的一个突出标记。
这种杀伤未感染激活 T 淋巴细胞的无 HLA 限制的 CTL 的 NKG2A(-)CD56(-)表型与在进行性 HIV 感染中发生的 CD8(+)T 淋巴细胞的普遍变化相匹配，表明这些表型变化可能反映了 CD8(+)T 细胞库的致病进化。这些 CTL 代表了具有潜在相关性的独特表型和功能亚群与 HIV 发病机制。
