Tamburini Beth, Doan Thu, Forward Tadg, Lucas Erin, Fleming Ira, Uecker-Martin Aspen, Hesselberth Jay, Morrison Thomas
University of Colorado Anschutz Medical Campus.
University of Colorado.
Res Sq. 2023 Sep 25:rs.3.rs-3307809. doi: 10.21203/rs.3.rs-3307809/v1.
Viral and vaccine antigens persist or are archived in lymph node stromal cells (LNSC) such as lymphatic endothelial cells (LEC) and fibroblastic reticular cells (FRC). Here, we find that, during the time frame of antigen archiving, LEC apoptosis caused by a second, but unrelated, innate immune stimulus such as vaccina viral infection or CpG DNA administration boosted memory CD8+ T cells specific to the archived antigen. In contrast to "bystander" activation associated with unrelated infections, the memory CD8+ T cells specific to the vaccine archived antigen were significantly higher than memory CD8+ T cells of a different antigen specificity. Finally, the boosted memory CD8+ T cells resulted in increased protection against expressing the vaccine antigen, but only for the duration that the vaccine antigen was archived. These findings outline a novel mechanism by which LNSC archived antigens, in addition to bystander activation, can augment memory CD8+ T cell responses during repeated inflammatory insults.
病毒和疫苗抗原会在淋巴结基质细胞（LNSC）中持续存在或被储存，如淋巴管内皮细胞（LEC）和成纤维网状细胞（FRC）。在此，我们发现，在抗原储存期间，由第二种但不相关的先天免疫刺激（如痘苗病毒感染或给予CpG DNA）引起的LEC凋亡增强了针对储存抗原的记忆性CD8⁺ T细胞。与与不相关感染相关的“旁观者”激活不同，针对疫苗储存抗原的记忆性CD8⁺ T细胞显著高于具有不同抗原特异性的记忆性CD8⁺ T细胞。最后，增强的记忆性CD8⁺ T细胞导致针对表达疫苗抗原的保护作用增强，但仅在疫苗抗原被储存的持续时间内。这些发现概述了一种新机制，通过该机制，LNSC储存的抗原除了旁观者激活外，还可在反复炎症刺激期间增强记忆性CD8⁺ T细胞反应。
