Innate memory of human Vγ2Vδ2 T cells: Distinct proliferative, migratory and tumorcidal capabilities of γδ memory subsets (52.17)

Abstract Human Vγ2Vδ2 T cells are unconventional T cells that monitor isoprenoid metabolism by using their antigen receptors to recognize foreign and self prenyl pyrophosphates. Although important for immunity to infections and for tumor immunotherapy, little is known about the development of γδ memory. Elucidation of γδ differentiation pathways will help to develop ways to boost their immunity. Here we report that there are many unique features compared with αβ T cells. Unlike αβ T cells, at birth half of Vγ2Vδ2 cells have memory phenotypes and ~25-40% express inflammatory chemokine receptors. In adults, 98.4% of Vγ2Vδ2 T cells are memory cells that can be separated into CD28+CD27+ TEarly (central); CD28+CD27- TEarly 27-; CD28-CD27+ TIntermediate (effector); and CD28-CD27- CD45RA+ TLate RA (effector) subsets. The memory subsets display distinct functional properties with differential expression of effector molecules, NK receptors, and chemokine receptors. Intermediate and late effector memory cells express higher levels of cytotoxic effector molecules, innate CXCR1, CXCR2, and CX3CR1 chemokine receptors, KIR, CD16, CD56, and CD57 NK receptors, and lower levels of the β7 integrin, and proliferate poorly compared with early memory cells that express CXCR6, CCR1, and CCR2. Thus, different inflammatory chemokines attract each Vγ2Vδ2 memory subset. The rapid conversion of Vγ2Vδ2 cells from naive to memory allows them to mount memory responses to primary bacterial and protozoan infections.