Archived antigen boosts CD8 T cell memory responses during an unrelated infection.

Abstract

Abstract Numerous studies have shown viral antigens can persist in lymph nodes after the resolution of the infection. We showed that lymphatic endothelial cells (LECs), which comprise the lymphatic vasculature, are the predominant cell type required for the persistence of antigen within the lymph node. We termed this process antigen archiving due to the ability of LECs to actively acquire and store antigens to which an active immune response occurred. This process involves antigen acquisition, retention, and exchange of the antigen between LECs and dendritic cells, resulting in the 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. We found that archived antigens could be released during an unrelated viral infection, during the time frame of LEC death. This release of antigen was visualized by a significant increase in archived antigen-specific endogenous or transferred memory CD8 T cells, but not memory T cells of an unrelated specificity. The increase in archived antigen-specific CD8 T cells maintained a more effector-like phenotype and performed significantly better upon antigenic challenge with Listeria monocytogenes (LM) expressing ovalbumin. Mice that received an unrelated infection 2–3 weeks prior to antigenic challenge demonstrated improved protection against LM-ova. In conclusion, archived antigen release during a secondary unrelated infection boosts the archived antigen-specific memory CD8 T cell population. These findings bring into question whether some previous data demonstrating heterologous immunity may be a result of archived antigen release. Supported by R01 AI121209 R21 AI155929