Abstract
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.
Highlights
Conventional T cells take on naive phenotypes when they emigrate out from the thymus, whereas innate T cells from the thymus are phenotypically of the effector/memory form [1].Compared with conventional T cells, these innate T cells, such as natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells and H2-M3-specific T cells, are selected by interaction with hematopoietic cells rather than thymic epithelial cells, and their development is dependent on IL–15 and the SAP (SLAM-associated protein) signaling pathway [1]
IL-4-induced innate CD8+ T cells are a unique subset of innate T cells that were recently identified in both mouse and PLOS Pathogens | DOI:10.1371/journal.ppat
This type of cells is not abundant in wild type C57BL/6 mice, they initially described in Tec-kinase-deficient mice [4,5] and subsequently found in the thymus of a variety of mice in which T-cell-associated genes are deficient [6,7,8,9,10,11,12,13] or CIITA-transgenic (CIITATg) mice in which MHC class II molecules are expressed in thymocytes [14]
Summary
Conventional T cells take on naive phenotypes when they emigrate out from the thymus, whereas innate T cells from the thymus are phenotypically of the effector/memory form [1].Compared with conventional T cells, these innate T cells, such as natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells and H2-M3-specific T cells, are selected by interaction with hematopoietic cells rather than thymic epithelial cells, and their development is dependent on IL–15 and the SAP (SLAM-associated protein) signaling pathway [1]. Eomes+ CD8+ T cells from both mice and human thymus exhibit immediate effector function upon TCR stimulation [6,14]; this type of CD8+ T cells has unique characteristics that make them different from MHC class Ib-restricted innate T cells. MHC class Ib-restricted innate T cells have a highly restricted TCR repertoire [16], whereas IL-4-induced Eomes+ innate CD8+ T cells from CIITATg mice have a diverse TCR repertoire very much like conventional T cells [14] This difference in TCR repertoire suggests that they are selected by diverse self-peptides presented by classical MHC class I molecules and raises the possibility that IL-4-induced innate CD8+ T cells perform some functions distinct from those of MHC class Ib-restricted innate T cells during a variety of immune responses. Little is known regarding the impact that the type of CD8+ T cells present during infection has on protection against viral persistence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
