Memory T cells contribute to early pathogen clearance in a site-specific manner in the absence of cognate antigen

Abstract

Abstract Memory CD8+ T lymphocytes are typically considered to contribute to host immunity when they reencounter their specific antigen; however, in the absence of cognate antigen, inflammatory signals can elicit the rapid expression of Granzyme B and Interferon-γ in memory CD8+ T cells. This is referred to as “bystander activation” and occurs during the early stages of infection, which are dominated by innate immune responses. We and others have demonstrated that bystander-activated cytotoxic T lymphocytes (BA-CTL) can kill target cells in an NKG2D-ssdependent, TCR-independent manner early after infection. This suggests that memory T cells can employ innate-like mechanisms for rapid TCR-independent responses to infection. Here we report that antigen non-specific BA-CTL display clustering and increased functionality at sites of splenic pathogen replication during WT Listeria monocytogenes (LM) infection. These clusters at early time-points closely resemble those of antigen-specific cells during primary and recall responses against recombinant LM. We describe the mechanisms driving this early activation and define distinct stages of this innate-like effector program. We propose that the purpose of recruiting BA-CTL to sites of infection and eliciting these innate-like functional capacities is to limit early pathogen replication.