Mechanisms underlying lineage commitment and plasticity of human γδ T cells

Abstract

Phenotypic and functional heterogeneity are the hallmarks of effector and memory T cells. Upon antigen stimulation, cd T cells differentiate into two major types of memory T cells: central memory cells, which patrol the blood and secondary lymphoid organs, and effector memory cells, which migrate to peripheral tissues. cd T cells display in vitro a certain degree of plasticity in their function that is reminiscent of that which is observed in conventional CD4 T cells. Similar to CD4 T cells, in which a plethora of specialized subsets affect the host response, cd T cells may readily and rapidly assume distinct Th1-, Th2-, Th17-, T FH and T regulatory-like effector functions, suggesting that they profoundly influence cell-mediated and humoral immune responses. In addition to differences in cytokine repertoire, cd T cells exhibit diversity in homing, such as migration to lymph node follicles, to help B cells versus migration to inflamed tissues. Here, we review our current understanding of cd T-cell lineage heterogeneity and flexibility, with an emphasis on the human system, and propose a classification of effector cd T cells based on distinct functional phenotypes.

The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells

“…[26][27][28][29][30][31] Antigen recognition by TCRcd is not major histocompatibility complexrestricted and is more similar to an 'antibody-like' response. [32][33][34][35] Therefore, using a CDR3d grafted TCRc9/d2-Fc fusion protein technology system, we constructed a TCRc9/ d2 (OT3)-Fc fusion protein to determine whether rHA binds directly to TCRcd.…”

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

“…In functional assays, Vc9/Vd2 T cell-matured DCs were able to polarize CD4 + T cells towards a Th1 phenotype as default pathway, characterized by increased IFN-c production and decreased IL-4 and IL-5 production [39][40][41]46]. However, given the functional plasticity of Vc9/Vd2 T cells [49], it remains to be investigated whether under certain conditions they may also instruct DCs to polarize naive CD4 + T cells toward other phenotypes (Th2, Th17, Th22, Treg). Futhermore, little is known about the potential of cd T cell-matured DCs to induce CD8 + T cell responses [50].…”

“…Depending on the culture conditions, Vc9/Vd2 T cells clearly assume different functions including distinct cytokine profiles [49,74,72,[124][125][126], and hence more research is needed to delineate whether Vc9/Vd2 T-APCs may induce different 'flavors' of CD4 + T cell responses (Th1, Th2, Th17, Th22, Treg), and what the signals involved in such a polarization are. In this respect, our preliminary findings suggest that under appropriate conditions Vc9/Vd2 T-APCs are able to induce considerable IL-22 expression in naive CD4 + T cells [C.J.T., M.E.…”

Human γδ Thymocytes Are Functionally Immature and Differentiate into Cytotoxic Type 1 Effector T Cells upon IL-2/IL-15 Signaling

“…It is therefore difficult to inquire where and how human gd T cells acquire their effector functions. In healthy individuals, these are tightly linked to IFN-g production, as alternative functional states, such as IL-17 or IL-22 secretion, are very rare (16)(17)(18).…”