Siebrecht M S, Hsia E, Spychalski C, Nagler-Anderson C
Mucosal Immunology Laboratory, Massachusetts General Hospital East Charlestown 02129.
Int Immunol. 1993 Jul;5(7):717-24. doi: 10.1093/intimm/5.7.717.
To gain insight into the specificity and function of intestinal intraepithelial lymphocytes (IEL), we have examined their response to staphylococcal enterotoxin B (SEB), a significant cause of food poisoning and a potent T cell mitogen. IEL include two populations of TCR alpha beta+ T cells. One of these resembles the T cells found in the Peyer's patch and is thymus dependent. The other subset is characterized by both TCR alpha beta and gamma delta+ IEL bearing a unique form of the CD8 molecule, expressed as an alpha alpha homodimer. CD8 alpha+ beta- IEL are thymus independent and appear to mature extrathymically in the gut epithelium. Two-color flow cytometric analysis showed that in vitro stimulation of IEL with SEB resulted in the expansion of the thymus dependent but not the thymus independent IEL; the CD8 alpha+ beta- IEL were functionally non-responsive to stimulation with SEB. 'Forbidden' self-superantigen reactive T cells present among IEL were also non-responsive to stimulation with SEB. The presence or absence of class II MHC molecules does not appear to play a role in the non-responsiveness to SEB, since CD8 alpha+ beta- IEL from class II deficient mice also failed to respond to stimulation with SEB. Depletion of CD8 beta+ and CD4+ T cells from total IEL decreased IL-2 production by IEL in response to cross-linking with anti-CD3, suggesting that the non-responsiveness of CD8 alpha+ beta- IEL extends to antigens other than SEB.
为深入了解肠道上皮内淋巴细胞(IEL)的特异性和功能,我们检测了它们对葡萄球菌肠毒素B(SEB)的反应,SEB是食物中毒的一个重要原因,也是一种有效的T细胞有丝分裂原。IEL包括两个TCRαβ + T细胞群体。其中一个类似于派尔集合淋巴结中发现的T细胞,依赖胸腺。另一个亚群的特征是同时具有TCRαβ和γδ + IEL,并带有一种独特形式的CD8分子,以αα同型二聚体形式表达。CD8α + β - IEL不依赖胸腺,似乎在肠道上皮中胸腺外成熟。双色流式细胞术分析表明,体外用SEB刺激IEL导致依赖胸腺的IEL而非不依赖胸腺的IEL扩增;CD8α + β - IEL对SEB刺激在功能上无反应。IEL中存在的“禁忌”自身超抗原反应性T细胞对SEB刺激也无反应。II类MHC分子的存在与否似乎在对SEB的无反应性中不起作用,因为来自II类缺陷小鼠的CD8α + β - IEL对SEB刺激也无反应。从总的IEL中去除CD8β + 和CD4 + T细胞会降低IEL在与抗CD3交联时产生IL - 2的能力,这表明CD8α + β - IEL的无反应性扩展到了SEB以外的抗原。