Spontaneous Proliferation of CD4+ T Cells in RAG-Deficient Hosts Promotes Antigen-Independent but IL-2-Dependent Strong Proliferative Response of Naïve CD8+ T Cells

Juhee Kim, Jun Young Lee, Kyungjin Cho, Sung Wook Hong, Kwang Soon Kim, Jonathan Sprent, Sin Hyeog Im, Charles D. Surh, Jae Ho Cho

Research output: Contribution to journalArticlepeer-review


The fast and intense proliferative responses have been well documented for naïve T cells adoptively transferred into chronic lymphopenic hosts. This response known as spontaneous proliferation (SP), unlike antigen-independent lymphopenia-induced proliferation (LIP), is driven in a manner dependent on antigens derived from commensal microbiota. However, the precise nature of the SP response and its impact on homeostasis and function for T cells rapidly responding under this lymphopenic condition are still unclear. Here we demonstrate that, when naïve T cells were adoptively transferred into specific pathogen-free (SPF) but not germ-free (GF) RAG−/− hosts, the SP response of these cells substantially affects the intensity and tempo of the responding T cells undergoing LIP. Therefore, the resulting response of these cells in SPF RAG−/− hosts was faster and stronger than the typical LIP response observed in irradiated B6 hosts. Although the intensity and tempo of such augmented LIP in SPF RAG−/− hosts were analogous to those of antigen-dependent SP, the former was independent of antigenic stimulation but most importantly, dependent on IL-2. Similar observations were also apparent in other acute lymphopenic settings where antigen-dependent T cell activation can strongly occur and induce sufficient levels of IL-2 production. Consequently, the resulting T cells undergoing IL-2-driven strong proliferative responses showed the ability to differentiate into functional effector and memory cells that can control infectious pathogens. These findings therefore reveal previously unappreciated role of IL-2 in driving the intense form of T cell proliferative responses in chronic lymphopenic hosts.

Original languageEnglish
Article number1907
JournalFrontiers in Immunology
Publication statusPublished - 2018 Aug 23

Bibliographical note

Funding Information:
We thank all the AIM/IBS laboratory members for both direct and indirect supporting; Haejin Jung and Me Ok Lee for assistance with cell sorting by flow cytometry; POSTECH Biotech Center animal facility for animal breeding, housing and supply; and all AIM/IBS administrative staffs. We thank Naomi Taylor and Valerie Dardalhon for helpful comments on this study. We thank Brian S. Sheridan for Listeria monocytogenes. This work was supported by project IBS-R005-D1 from the Institute for Basic Science, Korean Ministry of Science and Information/Communication/Technology.

Publisher Copyright:
© Copyright © 2018 Kim, Lee, Cho, Hong, Kim, Sprent, Im, Surh and Cho.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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