The Initial Draining Lymph Node Primes the Bulk of the CD8 T Cell Response and Influences Memory T Cell Trafficking after a Systemic Viral Infection

Abstract

Lymphocytic choriomeningitis virus (LCMV) causes a systemic infection in mice with virus replication occurring in both peripheral tissues and secondary lymphoid organs. Because of the rapid systemic dissemination of the virus, the secondary lymphoid organs responsible for the induction of the LCMV-specific CD8 T cell response are poorly defined. We show that the mediastinal lymph node (MedLN) serves as the primary draining lymph node following LCMV infection. In addition, we demonstrate that the MedLN is responsible for priming the majority of the virus-specific CD8 T cell response. Following resolution of the acute infection, the draining MedLN exhibits characteristics of a reactive lymph node including an increased presence of germinal center B cells and increased cellularity for up to 60 days post-infection. Furthermore, the reactive MedLN harbors an increased frequency of CD62L⁻ effector memory CD8 T cells as compared to the non-draining lymph nodes. The accumulation of LCMV-specific CD62L⁻ memory CD8 T cells in the MedLN is independent of residual antigen and is not a unique feature of the MedLN as footpad infection with LCMV leads to a similar increase of virus-specific CD62L⁻ effector memory CD8 T cells in the draining popliteal lymph node. Our results indicate that CD62L⁻ effector memory CD8 T cells are granted preferential access into the draining lymph nodes for an extended time following resolution of an infection. CD8 T cells are required for the elimination of infected host cells following an acute virus infection. In addition, memory CD8 T cells provide immunity to the host against a secondary infection. Much is known about the priming of CD8 T cells towards viruses that induce a localized infection, however the site responsible for priming the majority of CD8 T cells following a systemic viral infection remains unclear. Lymphocytic choriomeningitis virus (LCMV) induces an acute systemic viral infection when inoculated intraperitoneally, eliciting a robust CD8 T cell response. Although intraperitoneal LCMV infection results in rapid systemic viral replication, we demonstrate that the mediastinal lymph node (MedLN) serves as the initial draining lymph node and represents the primary site for the induction of the acute CD8 T cell response. In addition, we observe that CD62L⁻ effector memory CD8 T cells are preferentially recruited into the draining MedLN for up to 60 days following LCMV infection. Collectively, these studies indicate that the draining lymph node remains poised to defend the host against a secondary encounter with a pathogen for a prolonged time following the primary infection.