Selective Instructions for Memory T Cells

描述（由申请方提供）：粘液效应记忆CD 8 T细胞（TEM）位于粘膜上皮，具有增强的即时效应功能。相比之下，记忆T细胞驻留在淋巴组织内，需要增殖和分化才能成为迁移到上皮表面的效应细胞。TEM在病原体进入部位的积累对于保护性免疫是必不可少的，但是驱动粘膜记忆细胞分化的机制知之甚少。我们的初步数据表明，由高亲和力/亲合力TCR信号诱导的活化诱导的CD 8aa可以选择性地将胸腺细胞和成熟的CD 8 T细胞从活化诱导的细胞死亡（AICD）中拯救出来，使它们成为记忆T细胞。此外，我们的数据还表明，高亲和力的CD 8aa配体，小鼠胸腺白血病（TL）抗原，诱导一些APC和肠上皮细胞组成型表达，可能作为第二个选择性的关键组成部分，以确保长期积累的最适合的效应细胞（CD 8aa+）形成粘膜TEM。目前的提案旨在为这些令人兴奋的、突破性的和非常重要的初步观测提供坚实的证据。

DESCRIPTION (provided by applicant): Mucosal effector memory CD8 T cells (TEM) are located at mucosal epithelium and have a heightened and immediate effector function. By contrast, memory T cells residing within lymphoid tissues and require proliferation and differentiation to become effector cells that migrate to epithelial surfaces. The accumulation of TEM at the pathogen entry site(s) is essential for protective immunity, but the mechanisms that drive the differentiation of mucosal memory cells are poorly understood. Our preliminary data indicate that activation-induced CD8aa, induced by high affinity/avidity TCR signals, might selectively rescue thymocytes and mature CD8 T cells from activation induced cell death (AICD) allowing them to become memory T cells. Furthermore, our data also suggest that the high-affinity CD8aa ligand, the mouse thymus leukemia (TL) antigen, induced on some APCs and constitutively expressed on intestinal epithelial cells, might serve as a second selective key component to assure the long-term accumulation of the fittest effector cells (CD8aa+) to form mucosal TEM. The current proposal is designed to provide solid evidence for these exciting, breakthrough and highly significant initial observations.