γδ T cell effector functions: a blend of innate programming and acquired plasticity (original) (raw)

2010, Nature Reviews Immunology

The integrity of higher vertebrates is maintained through protective mechanisms that can detect stress-induced determinants that arise following infection, injury or cellular alterations. This surveillance involves both innate and adaptive immune processes. Innate responses, mainly mediated by natural killer (NK) cells and myelomonocytic cells, are readily activated following engagement of non-clonal receptors referred to as pattern recognition receptors (PRRs), which are specific for determinants that are broadly expressed by microorganisms or are upregulated by host cells in response to cell stress 1,2. PRR engagement triggers an inflammatory response that initially leads to increased microbicidal and cytotoxic functions of immune cells, and clearance of the eliciting agent, and later to tissue repair and immune downmodulation 3. Adaptive immune cells have overall functions that are similar to those of innate cells but, owing to immuno logical memory, they can yield stronger and faster responses after repeated exposure to a given eliciting agent 4. The establishment of immunological memory implies expansion of T and B cells, specific for the eliciting antigen, after engagement of clonally distributed T cell receptors (TCRs) and B cell receptors (BCRs). Clonally expanded T and B cell populations acquire a restricted set of effector functions that are presumably best suited for clearance of the eliciting agent at a given time point in a given tissue. Innate cells are involved in the induction of adaptive immune responses of appropriate strength, kinetics and function in two ways. First, they efficiently internalize pathogens and dying cells and process them into peptide antigens that are presented in the context of MHC molecules to conventional αβ T cells. Second, they integrate danger and inflammatory cues and translate them into stimuli that lead to proper functional polarization of αβ T cell and B cell responses 4. Although, generally, innate immune responses precede adaptive immune responses, a reverse interplay from adaptive to innate immune effectors also contributes to the early recruitment and activation of innate immune cells and subsequent functional polarization of MHC-restricted T cells. T cells contributing to this reverse crosstalk involve subsets of αβ T cells restricted by the non-polymorphic MHC class I-like molecules CD1d and MHC-related protein 1 (MR1) (known as invariant NKT cells and mucosa-associated invariant T cells, respectively), as well as T cells expressing γδ TCRs 5,6. These lympho cytes have been termed non-conventional, innate-like or transitional T cells, owing to several distinguishing features that are shared with innate immune cells 5,7. Similar to other non-conventional T cells, γδ T cells recognize conserved non-peptide antigens that are upregulated by stressed cells, the expression modalities and distribution of which resemble those of pathogenassociated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) recognized by PRRs. These cells acquire a pre-activated phenotype associated with the upregulation of memory markers early in their development. This pre-activated status allows rapid induction of effector functions following the detection of tissue stress. Another important feature of γδ T cells is their tropism for epithelial surfaces, such as those of the liver and skin, and mucosae from respiratory, digestive and reproductive