Memory-phenotype CD4+ T cells spontaneously generated under steady-state conditions exert innate TH1-like effector function

Takeshi Kawabe; Dragana Jankovic; Shuko Kawabe; Yuefeng Huang; Ping-Hsien Lee; Hidehiro Yamane; Jinfang Zhu; Alan Sher; Ronald N Germain; William E Paul

doi:10.1126/sciimmunol.aam9304

Memory-phenotype CD4⁺ T cells spontaneously generated under steady-state conditions exert innate T_H1-like effector function

Sci Immunol. 2017 Jun 16;2(12):eaam9304. doi: 10.1126/sciimmunol.aam9304.

Authors

Takeshi Kawabe^{1

2}, Dragana Jankovic², Shuko Kawabe³, Yuefeng Huang³, Ping-Hsien Lee³, Hidehiro Yamane³, Jinfang Zhu⁴, Alan Sher⁵, Ronald N Germain^{1

6}, William E Paul³

Affiliations

¹ Cytokine Biology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. [email protected] [email protected] [email protected].
² Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
³ Cytokine Biology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. [email protected] [email protected] [email protected].
⁶ Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Conventional CD4⁺ T cells are composed of naïve, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) cells under steady state. Naïve and pathogen-specific memory cells play key roles in adaptive immunity, whereas the homeostatic mechanisms regulating the generation of MP cells and their biological functions are unclear. We show that MP cells are autonomously generated from peripheral naïve cells in the absence of infectious stimulation in a T cell receptor (TCR)- and CD28-dependent manner. We further demonstrate that MP cells contain a T-bet^hi subpopulation that is continuously generated by environmental interleukin-12 (IL-12) and rapidly produces interferon-γ (IFN-γ) in response to IL-12 in the absence of pathogen recognition. These cells can provide nonspecific host resistance against Toxoplasma gondii infection while enhancing the adaptive CD4⁺ T cell responses. Together, these findings reveal that MP cells are continuously generated from naïve precursors and have a previously undescribed innate immune function by which they produce an early, T helper cell type 1 (T_H1)-like protective response against pathogens.

Grants and funding

Z99 AI999999/Intramural NIH HHS/United States