Immunology Research Group and Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alta., Canada.
Eur J Immunol. 2010 Feb;40(2):449-59. doi: 10.1002/eji.200939586.
Adenosine has long been regarded as a crucial anti-inflammatory agent that protects the host from excessive damage. It has been reported to play an important role in suppressing immune activation, particularly that of T cells. However, it is a general observation that induction of T-cell activation is an efficient event despite the high adenosine levels that are often present in the affected host due to injury or stress. We report here that prior to antigenic stimulation via TCR/CD3, exposure of T cells to adenosine desensitizes adenosine receptors, so as to create a window of time where the T cells are insensitive to this ubiquitous suppressor. T cells from mice that were pre-exposed to this manipulation showed stronger responses to antigenic stimulation; therefore, the P1 adenosine receptor desensitization demonstrated an adjuvant-like effect. Our results suggest that adenosine receptor desensitization may be a mechanism for T cells to escape the general suppression during early points of T-cell activation and may emerge as a potential alternative for vaccine adjuvants.
腺苷长期以来一直被视为一种关键的抗炎剂，可以保护宿主免受过度损伤。据报道，它在抑制免疫激活方面发挥着重要作用，特别是在抑制 T 细胞方面。然而，尽管由于损伤或应激，受影响的宿主中通常存在高水平的腺苷，但诱导 T 细胞激活是一种有效的事件，这是一个普遍的观察结果。我们在这里报告，在通过 TCR/CD3 进行抗原刺激之前，T 细胞暴露于腺苷会使腺苷受体脱敏，从而创造一个 T 细胞对这种无处不在的抑制剂不敏感的时间窗口。预先接受这种操作的小鼠 T 细胞对抗原刺激的反应更强；因此，P1 腺苷受体脱敏表现出佐剂样作用。我们的结果表明，腺苷受体脱敏可能是 T 细胞在 T 细胞激活早期逃避普遍抑制的一种机制，并可能成为疫苗佐剂的一种潜在替代方法。
