A Requirement for the Vγ1+ Subset of Peripheral γδ T Cells in the Control of the Systemic Growth of Toxoplasma gondii and Infection-Induced Pathology

Abstract

γδ T cells are a diverse population of T cells that are widely distributed and are a common feature of pathogen-induced immune responses. It is not clear, however, whether different populations of γδ T cells have specific functions, and what factors determine the functional properties of individual populations. A murine model of peroral Toxoplasma gondii infection was used to determine the contribution Vγ1+ intestinal intraepithelial lymphocytes (IELs) vs systemic Vγ1+ T cells make to the acute and chronic stages of the host immune response, and whether the macrophage cytocidal activity of Vγ1+ T cells described in bacterial infections is seen in other, unrelated infectious disease models. In response to oral infection with virulent type 1 or avirulent type II strains of T. gondii, TCR-δ−/− mice rapidly developed severe ileitis. In contrast, in mice deficient in Vγ1+ T cells and IELs and wild-type mice, inflammation was delayed in onset and less severe. The protective effect of (Vγ1−) IELs to Toxoplasma infection was unrelated to their cytolytic and cytokine (Th1)-producing capabilities. Systemic Vγ1+ T cells were shown to play an essential role in limiting parasite growth and inflammation in peripheral tissues and, in particular, in the CNS, that was associated with their ability to efficiently kill parasite-elicited and infected macrophages. These findings suggest that macrophage cytocidal activity of Vγ1+ T cells may be a universal feature of pathogen-induced immune responses and that microenvironmental factors influence the involvement and function of γδ T cells in the host response to infection.

A subset of IL‐10‐producing γδ T cells protect the liver from Listeria‐elicited, CD8+ T cell‐mediated injury

“…Although these opposing functions of Vc4 T cells in different disease models are difficult to reconcile, they may reflect the functional heterogeneity of individual subsets of cd T cells. Consistent with this are the results of analysing the involvement of Vc1 T cells throughout the course of Listeria infection, demonstrating that their function is temporally heterogeneous and influenced by local environmental factors [3,32]. In conclusion, our findings support a model of hepatoprotection by cd T cells in which the pathogenic potential of effector TNF-a-producing CD8 + T cells is controlled as a result of their interaction with and activation of Vc4 T cells that in an IL-10-dependent manner act to regulate their growth and TNF-a production.…”

“…Inflammation in the liver has multiple aetiology, from the direct infection of hepatocytes with viruses, bacteria or parasites [1][2][3], to transient ischemia [4]. Inflammation is a normal process for removing infection and repairing tissue damage, which in the liver involves both resident and recruited macrophages, neutrophils, NK cells and T cells [5].…”

γδ T Cells and Their Potential for Immunotherapy

“…γδ T cells not only play protective roles in viral and bacterial infections, but also control infections by protozoas such as Leishmania 160 and Toxoplasma gondii 161, whereas the γδ T cell-mediated inflammation may cause some unwanted destruction of surrounding tissues. Similarly, the protective roles of γδ T cells during malaria infection have been confirmed in several independent studies 162.…”

Roles of IFN-γ and γδ T Cells in Protective Immunity Against Blood-Stage Malaria

“…On the other hand, αβ T cells, such as CD4 + helper T cells and CD8 + killer T cells, are typically related to adaptive immunity. γδ T cells play critical roles in protective immune responses against protozoan parasites, bacteria, and viruses that are associated with various infectious diseases (26–32). This review focuses on the protective abilities of γδ T cells and IFN-γ in the response against malaria infection.…”