Peakman Mark
Department of Immunobiology, King's College London, School of Medicine at Guy's, King's College & St Thomas' Hospitals, Guys Hospital, London SE1 9RT, UK.
Novartis Found Symp. 2008;292:113-9; discussion 119-29, 202-3. doi: 10.1002/9780470697405.ch9.
The intra-islet cellular infiltrate found at post mortem in patients with new-onset Type 1 diabetes mellitus (T1DM) comprises both CD4+ and CD8+ cells, yet very few studies have investigated CD8 T cell responses to islet autoantigens. We therefore examined the response of peripheral blood CD8 T cells from new-onset T1DM patients and control subjects possessing HLA-A0201 genes to potential CD8 T cell epitopes contained in a panel of peptides derived from proinsulin, glutamic acid decarboxylase, islet-specific glucose-6-phosphatase catalytic subunit-related protein and islet amyloid polypeptide, each putatively presented by the HLA class I molecule, HLA-A2.1 (A0201) using a variety of techniques including in vitro culture with peptide, enzyme-linked immunospot (ELISPOT) assay and HLA tetramers. We find CD8 T cells present using these techniques, some of which have cytotoxic activity. The demonstration that rare islet autoreactive CD8 T cells are detectable in blood should promote mechanistic studies on these cells, as well as advancing T cell assay development.
在新诊断的1型糖尿病（T1DM）患者尸检时发现的胰岛内细胞浸润包含CD4+和CD8+细胞，但很少有研究调查CD8 T细胞对胰岛自身抗原的反应。因此，我们检测了新诊断的T1DM患者和具有HLA - A0201基因的对照受试者外周血CD8 T细胞对一组源自胰岛素原、谷氨酸脱羧酶、胰岛特异性葡萄糖-6-磷酸酶催化亚基相关蛋白和胰岛淀粉样多肽的肽段中潜在CD8 T细胞表位的反应，这些肽段假定由HLA I类分子HLA - A2.1（A0201）呈递，采用了多种技术，包括与肽段进行体外培养、酶联免疫斑点（ELISPOT）分析和HLA四聚体技术。我们发现利用这些技术可检测到CD8 T细胞，其中一些具有细胞毒性活性。在血液中可检测到罕见的胰岛自身反应性CD8 T细胞这一发现，应能推动对这些细胞的机制研究，并促进T细胞检测方法的发展。
