Adaptive immune responses mediated by natural killer cells

Abstract

Adaptive immunity has traditionally been considered a unique feature of vertebrate physiology. Unlike innate immune responses, which remain essentially unchanged upon exposure to a recurrent challenge with the same stimulus, adaptive immune cells possess the ability to learn and remember. Thus, secondary adaptive responses to a previously encountered challenge are qualitatively and/or quantitatively distinct from those elicited by a primary encounter. Besides this capacity to acquire long-lived memory, the second cardinal feature of adaptive immunity is antigen specificity. It has been generally believed that only T and B cells can develop antigen-specific immunologic memory, because these lymphocytes uniquely express recombination-activating gene (RAG) proteins, which are necessary for somatic rearrangement of V(D)J gene segments to assemble diverse antigen-specific receptors. However, recent work has uncovered discrete subsets of murine natural killer (NK) cells capable of mediating long-lived, antigen-specific recall responses to a variety of hapten-based contact sensitizers. These NK cells appear to use distinct, RAG-independent mechanisms to generate antigen specificity. Murine NK cells have also recently been shown to develop memory upon viral infection. Here, we review recent evidence indicating that at least some NK cells are capable of mediating what appears to be adaptive immunity and discuss potential mechanisms that may contribute to RAG-independent generation of antigenic diversity and longevity.

Fig. 1. Sensitized Thy1+ NK cells accumulate at sites of challenge

C57BL/6 mice were sensitized by abdominal painting with DNFB or hapten-free solvent (acetone) as a control on days 0 and 1, and one ear was challenged with DNFB on day 4, while the opposite ear was concomitantly treated with acetone. Ears were harvested at indicated time points after challenge, and single cell suspensions were analyzed by flow cytometry for the presence of NK cells. Thy1 and NK1.1 staining is shown after gating on CD45⁺TCRβ⁻cells.

Fig. 2

Schematic representation of the sequence of events leading to hapten-specific NK memory in CHS.