Bystander-activated memory T lymphocytes cluster around infected cells early after infection

Abstract

Abstract Innate and adaptive immune responses are typically considered to occur sequentially following an infection. The innate immune system responds initially to an infection and the antigen-specific T and B cell response develops subsequently. Although the peak of the antigen-specific T cell response lags days behind the innate response, inflammatory signals lead to rapid expression of Granzyme B and Interferon-γ in memory CD8+ T cells. This occurs in a T cell receptor (TCR) independent manner and is referred to as “bystander activation.” We and others have demonstrated that these bystander-activated cytotoxic T lymphocytes (BA-CTL) can kill target cells in an NKG2D-dependent, TCR-independent fashion early after infection. This suggests that T cells use innate-like mechanisms for rapid TCR-independent responses to infection. Here we report that during WT Listeria monocytogenes (LM) infection, antigen non-specific BA-CTL rapidly migrate to cluster around infected cells, surrounding foci of LM in splenic white pulp at 24h post infection. These clusters at early time-points closely resemble antigen-specific effector T cell clustering on day 7 post-infection. We describe the mechanisms driving this early activation and define distinct stages of this innate-like effector program. We propose that the purpose of driving bystander-activated T cells to sites of infection and eliciting these innate-like functional capacities is to limit early pathogen replication.