Cross-presenting human γδ T cells induce robust CD8 ⁺ αβ T cell responses

Abstract

anti-microbial immunity ͉ antigen cross-presentation

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

“…Expression of HLA-DR is a well known attribute of activated T cells, and such activated T cells may be able to present antigens in appropriate contexts [117]. However, only Vc9/Vd2 T cells have been shown to be able to act as truly professional APCs, as characterized by the effective uptake and processing of exogenous antigens through endocytosis [118] and even phagocytosis [119], and the priming and differentiation of naive CD4 + and CD8 + T cells [116,120] (Fig. 1).…”

“…and B.M., unpublished], supporting an unexpected plasticity in Vc9/Vd2 T cell-driven CD4 + T cell responses. The true potential of Vc9/Vd2 T-APCs as novel type of professional APC becomes apparent when considering their capacity to take up soluble proteins from the microenvironment and load antigenic peptides onto newly translated MHC class I molecules for efficient presentation to CD8 + T cells, in a mechanism usually referred to as antigen cross-presentation [120]. Activated Vc9/ Vd2 T cells turned out to be well equipped cross-presenting APCs capable of processing not only defined proteins but also complex material such as cell debris and whole bacteria, and shuttle endocytosed antigens into the cytosol for degradation by the proteasome [118][119][120].…”

“…The true potential of Vc9/Vd2 T-APCs as novel type of professional APC becomes apparent when considering their capacity to take up soluble proteins from the microenvironment and load antigenic peptides onto newly translated MHC class I molecules for efficient presentation to CD8 + T cells, in a mechanism usually referred to as antigen cross-presentation [120]. Activated Vc9/ Vd2 T cells turned out to be well equipped cross-presenting APCs capable of processing not only defined proteins but also complex material such as cell debris and whole bacteria, and shuttle endocytosed antigens into the cytosol for degradation by the proteasome [118][119][120]. As Vc9/Vd2 T cells retain their cytolytic potential when they acquire APC functions [127], this unique combination of direct target cytotoxicity and APC machinery allows for scenarios in which Vc9/Vd2 T cells would lyse transformed, stressed or infected cells, and take up and process released proteins for presentation to both CD4 + and CD8 + T cells, with enormous implications for novel immunotherapies and vaccines [128][129][130][131][132].…”

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

“…[13][14][15] However, the versatility of cd T cells is further extended by their demonstrated ability to assume the role and appearance of professional antigen presenting cells. 16,17 This unusual functional plasticity has given the impression that these multitalented T cells are 'Jacks of all-trades, but masters of none', and they are sometimes erroneously delegated to a niche occupied by vestigial …”

γδ-T cells: an unpolished sword in human anti-infection immunity

“…In addition to their direct anti-infection activities, human cd-T cells act as professional APCs and take up, process and present pathogen-related antigens from both free viral particles 29 and infected cells 57,105 to other effector immune cells. 106,107 These cd-T APCs express approximately similar levels of HLA-DR and CD80/ CD86 compared to traditional APCs 29 and induce NK cell activation, 108,109 antigen-specific ab-T-cell responses 29,107 and even antibody production. 67 Although the physiological roles of cd-T APCs still need to be illuminated by more in vivo studies, recent investigations of murine cd-T cells have confirmed the general existence of cd-T APCs.…”