Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

Abstract

γδ T cells are fascinating cells that bridge the innate and adaptive immune systems. They have long been known to proliferate rapidly following infection; however, the identity of the specific γδ T cell subsets proliferating and the role of this expansion in protection from disease have only been explored more recently. Several recent studies have investigated γδ T‐cell responses to vaccines targeting infections such as Mycobacterium, Plasmodium and influenza, and studies in animal models have provided further insight into the association of these responses with improved clinical outcomes. In this review, we examine the evidence for a role for γδ T cells in vaccine‐induced protection against various bacterial, protozoan and viral infections. We further discuss results suggesting potential mechanisms for protection, including cytokine‐mediated direct and indirect killing of infected cells, and highlight remaining open questions in the field. Finally, building on current efforts to integrate strategies targeting γδ T cells into immunotherapies for cancer, we discuss potential approaches to improve vaccines for infectious diseases by inducing γδ T‐cell activation and cytotoxicity.

How to Train Your Dragon: Harnessing Gamma Delta T Cells Antiviral Functions and Trained Immunity in a Pandemic Era

“…Another known mechanism of in vivo gd T cell activation is by microbial products like listeria, mycobacteria or salmonelladerived vaccines (214)(215)(216). Indeed, there is accumulating evidence that innate immunity, including gd T cells, is boosted by specific vaccination in addition to targeted adaptive immunity (217). For example, the influenza vaccine is able to induce virusspecific gd T cell expansion along with CD4+ and CD8+ T cells stimulation (218), and the differentiation of these gd T cells into an effector/memory phenotype, with increased perforin expression (219).…”

Making a case for using γδ T cells against SARS-CoV-2

“…Hence, a BP-based therapeutic strategy may facilitate novel approaches to the treatment of COVID-19 infection (Poccia et al 2006). In addition, considering the evidences for the role of cd T cells in vaccine-induced protection to viral infections such as influenza (Dantzler et al 2019), incorporating them into a vaccine strategy could be beneficial in COVID-19. Further understanding of the role of cd T cells in homeostasis and pathogen elimination will shed light on potential novel vaccines and therapies.…”

Patients with gastrointestinal irritability after TGN1412-induced cytokine storm displayed selective expansion of gut-homing αβ and γδT cells

“…It is also now widely recognized that Vδ2 + T cells display tissue-tropic phenotypes consistent with trafficking to barrier sites where pAg-producing microbes and tumors frequently originate [ 29 , 30 ]. In particular, Vδ2 + T cells are associated with effective host immunity to pAg-producing mycobacteria and robust responses to bacillus Calmette–Guérin (BCG) vaccination [ 42 , 43 ], which induces population expansion and upregulation of CD69 and IFNγ expression in vitro. Notably, these responses are enhanced in BCG responders compared with non-sensitized controls [ 44 , 45 ], and the pool of Vδ2 + T cells generated lacks lymph node homing receptors while displaying homogenous expression of CD28 [ 45 ].…”