IL-4 Induced Innate CD8+ T Cells Control Persistent Viral Infection

Memory-like CD8+ T cells expressing eomesodermin are a subset of innate T cells initially identified in a number of genetically modified mice, and also exist in wild mice and human. The acquisition of memory phenotype and function by these T cells is dependent on IL–4 produced by PLZF+ innate T cells; however, their physiologic function is still not known. Here we found that these IL-4-induced innate CD8+ T cells are critical for accelerating the control of chronic virus infection. In CIITA-transgenic mice, which have a substantial population of IL-4-induced innate CD8+ T cells, this population facilitated rapid control of viremia and induction of functional anti-viral T-cell responses during infection with chronic form of lymphocytic choriomeningitis virus. Characteristically, anti-viral innate CD8+ T cells accumulated sufficiently during early phase of infection. They produced a robust amount of IFN-γ and TNF-α with enhanced expression of a degranulation marker. Furthermore, this finding was confirmed in wild-type mice. Taken together, the results from our study show that innate CD8+ T cells works as an early defense mechanism against chronic viral infection.
Author Summary Over the course of viral infection there may be a limited time period during which the host system can eliminate the virus. When viruses are not eliminated within this period of time, virus can establish persistent infection. Here, we show that IL-4-induced innate CD8+ T cells are able to effectively control chronic virus infection. Innate T cells are heterogeneous population of T cells that acquire effector/memory phenotype as a result of their maturation process in thymus, unlike conventional T cells that differentiate into memory cells after antigen encounter in periphery. Previous data suggest that innate T cells might serve as a first-line of defense against certain bacterial pathogens. IL-4-induced innate CD8+ T cells are a unique subset of innate T cells that were recently identified in both mouse and human. We found that IL-4-induced innate CD8+ T cells immediately accumulated after viral infection and produced a robust amount of effector cytokines. Thereby, IL-4-induced innate CD8+ T cells provide an effective barrier to the establishment of persistent infection via effective virus control during the early phase of viral infection. Collectively our data show that IL-4-induced innate CD8+ T cells works as an early defense mechanism against chronic viral infection.