Selective Instructions for Memory T Cells

描述(申请人提供)：粘膜效应记忆CD8 T细胞位于粘膜上皮细胞，具有增强的即刻效应功能。相比之下，位于淋巴组织内的记忆T细胞需要增殖和分化才能成为迁移到上皮表面的效应细胞。在病原体进入部位(S)积累的透射电子显微镜对于保护性免疫是必不可少的，但驱动粘膜记忆细胞分化的机制尚不清楚。我们的初步数据表明，由高亲和力/亲和力TCR信号诱导的激活诱导的CD8aa可能选择性地将胸腺细胞和成熟的CD8T细胞从激活诱导的细胞死亡(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CD8aa配体，即小鼠胸腺白血病(TL)抗原，在一些APC上诱导并在肠上皮细胞上结构性表达，可能是确保最适合的效应细胞(CD8aa+)长期积累以形成粘膜透射电子显微镜的第二个选择性关键成分。目前的提议旨在为这些令人兴奋的、突破性的和非常重要的初步观察提供坚实的证据。

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.