Antigen archiving promotes secondary CD8+ T cell memory responses during an unrelated infection

Abstract

Abstract Numerous studies have shown viral antigens can persist in lymph nodes after resolution of the infection. We showed that lymphatic endothelial cells (LECs), which comprise the lymphatic vasculature necessary for antigen drainage from the tissue, is the predominant cell type required for the persistence of antigen within the lymph node. We termed this process antigen archiving due the ability of LECs to actively archive antigens to which an immune response has occurred. This process involves antigen acquisition, retention, and exchange of the antigen between LECs and dendritic cells (DC), resulting in presentation of the archived antigens to CD8+ memory T cells and improving effector function. In more recent data, we demonstrated that LEC death causes the release of archived antigens during LN contraction. The objective of this study was to determine if during a secondary unrelated infection whether LEC death would occur and cause archived antigens to be released. As expected, we found that a second and unrelated viral infection causes LEC death within two to three weeks following infection. Within the same time frame that we observed LEC death, we observed a significant increase in archived antigen-specific endogenous memory T cells. This increase only occurred in mice that received an unrelated viral infection and not in those mice that did not receive the unrelated viral infection. In conclusion, archived antigen release during a secondary unrelated infection potentially boosts the archived antigen specific memory CD8+ T cell population. Understanding the mechanism of antigen release during multiple infections could ultimately lead to better strategies for vaccination and improve our understanding of how LECs influence immunity.