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

Ara Lee; Seung Pyo Park; Chan Hee Park; Byung Hyun Kang; Seong Hoe Park; Sang-Jun Ha; Kyeong Cheon Jung

doi:10.1371/journal.ppat.1005193

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

PLoS Pathog. 2015 Oct 9;11(10):e1005193. doi: 10.1371/journal.ppat.1005193. eCollection 2015 Oct.

Authors

Ara Lee¹, Seung Pyo Park², Chan Hee Park¹, Byung Hyun Kang³, Seong Hoe Park⁴, Sang-Jun Ha¹, Kyeong Cheon Jung⁵

Affiliations

¹ Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
² Transplantation Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
³ Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁴ Transplantation Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea; Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁵ Transplantation Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea; Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
CD8-Positive T-Lymphocytes / immunology*
Cell Separation
Chronic Disease
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Immunity, Innate / immunology*
Immunophenotyping
Interleukin-4 / immunology*
Lymphocytic Choriomeningitis / immunology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
T-Lymphocyte Subsets / immunology*

Substances

Interleukin-4

Grants and funding

This work was partly supported by grants from the National Research Foundation (NRF) of Korea (2012M3A9A8053249 to SHP and KCJ). This work was also supported by the Research Resettlement Fund for the New Faculty of Seoul National University in 2013 (to KCJ), the Basic Science and Research Program (2013R1A1A2010389 to SJH) and Bio & Medical Technology Development Program (2012M3A9B4028264 to SJH) of the National Research Foundation of Korea (NRF) funded by the Korea government (MEST), and a grant from the Korean Health Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (HI14C2680 to SJH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.