The PPARα pathway in Vγ9Vδ2 T cell anergy

The Balance Between Donor T Cell Anergy

Molecular regulation of T-cell anergy.

The activation of T cells is tightly controlled by many positive and negative regulatory processes. This fine-tuning allows productive immunity to pathogens while minimizing the risk of autoimmunity. One negative regulatory mechanism is clonal anergy, which is a hyporesponsive state that occurs when T cells are activated through the T-cell antigen receptor in the absence of appropriate co-stimu...

Prevention of Vγ9Vδ2 T Cell Activation by a Vγ9Vδ2 TCR Nanobody.

Vγ9Vδ2 T cell activation plays an important role in antitumor and antimicrobial immune responses. However, there are conditions in which Vγ9Vδ2 T cell activation can be considered inappropriate for the host. Patients treated with aminobisphosphonates for hypercalcemia or metastatic bone disease often present with a debilitating acute phase response as a result of Vγ9Vδ2 T cell activation. To da...

Ecto-ATPase CD39 Inactivates Isoprenoid-Derived Vγ9Vδ2 T Cell Phosphoantigens.

In humans, Vγ9Vδ2 T cells respond to self and pathogen-associated, diphosphate-containing isoprenoids, also known as phosphoantigens (pAgs). However, activation and homeostasis of Vγ9Vδ2 T cells remain incompletely understood. Here, we show that pAgs induced expression of the ecto-ATPase CD39, which, however, not only hydrolyzed ATP but also abrogated the γδ T cell receptor (TCR) agonistic acti...

BTLA, a key regulator of Vγ9Vδ2 T-cell proliferation

Although in the last few years γδ T lymphocytes have been the subject of growing interest as potential anticancer immunotherapeutics, how the proliferative and effector responses of these cells are regulated remains unclear. We have recently reported that the co-receptor B and T lymphocyte associated (BTLA) inhibits the proliferation of human Vγ9Vδ2 T cells, potentially underpinning a mechanism...