NK Cell Memory
Natural killer (NK) cells were discovered over 40 years ago as a population of lymphocytes that could lyse sheep red blood cells and tumor cells “naturally” (i.e.without requiring prior activation). Traditionally, NK cells have been classified as innate immune cells that recognize their targets through a variety of germqline-encoded receptors. However, our laboratory discovered that a subset of NK cells has the capacity to mediate long-lived, antigen-specific adaptive immunity (Paust and von Andrian, 2011). We are currently employing a wide variety of investigative lines, including genetic, bioinformatic, cellular, and biochemical approaches to identify the molecular mechanism(s) underlying NK cell-mediated adaptive immunity.
Ready to Recruit: Leukocyte Trafficking
Viral acute infections induce pathogen-specific T cell activation and differentiation into heterogeneous effectors that give rise to different memory subsets. We are interested in untangling the cell-fate decisions and lineage relationships that underlie the effector-to-memory transition as well as the maintenance of memory subsets. In this regard, we have identified the chemokine receptor CX3CR1 as a key marker to distinguish three distinct CD8+ T effector and memory subsets (negative, intermediate and high) that differ in phenotypic characteristics, trafficking properties and specialized functions. This finding has allowed us to reformulate the long-held paradigm of central (CX3CR1neg) vs. effector (CX3CR1high) memory cells by including now the peripheral memory (CX3CR1int) cells that are chiefly responsible for the global surveillance of non-lymphoid tissues (Gerlach et al., Immunity 2016).
The immune system has evolved to protect the host from infectious agents, parasites and tumor growth, and to assure the maintenance of homeostasis. Similarly, the primary function of the somatosensory branch of the peripheral nervous system is to provide sensory information about the environment, allowing the organism to react to and avoid situations, which could otherwise have deleterious effects. Consequently, it follows that the two systems should cooperate and, indeed, multiple recent studies have revealed an exciting, context-specific interaction between the immune system and the peripheral nervous system in multiple tissues.
To gain detailed insights into the underlying molecular and cellular mechanisms involved in this neuroimmune crosstalk, we are using a wide variety of approaches ranging from biochemistry and in vitro culture systems to state of the art imaging and single-cell RNA sequencing techniques. Our ultimate goal is to broaden our knowledge of the neuroimmune interactions and to open new, previously unappreciated avenues of research.