IL-7 is critical for homeostatic proliferation and survival of naïve T cells

doi:10.1073/pnas.161126098

IL-7 is critical for homeostatic proliferation and survival of naïve T cells

^*Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037; Departments of ^†Molecular Microbiology and Immunology and ^§Pediatrics, Children's Hospital, University of Southern California–Keck School of Medicine, Los Angeles, CA 90027; and ^‡Eos Biotechnology, South San Francisco, CA 94080

Edited by Howard M. Grey, La Jolla Institute for Allergy and Immunology, San Diego, CA, and approved June 5, 2001 (received for review March 14, 2001)

Abstract

In T cell-deficient conditions, naïve T cells undergo spontaneous “homeostatic” proliferation in response to contact with self-MHC/peptide ligands. With the aid of an in vitro system, we show here that homeostatic proliferation is also cytokine-dependent. The cytokines IL-4, IL-7, and IL-15 enhanced homeostatic proliferation of naïve T cells in vitro. Of these cytokines, only IL-7 was found to be critical; thus, naïve T cells underwent homeostatic proliferation in IL-4⁻ and IL-15⁻ hosts but proliferated minimally in IL-7⁻ hosts. In addition to homeostatic proliferation, the prolonged survival of naïve T cells requires IL-7. Thus, naïve T cells disappeared gradually over a 1-month period upon adoptive transfer into IL-7⁻ hosts. These findings indicate that naïve T cells depend on IL-7 for survival and homeostatic proliferation.

Footnotes

↵ ¶ To whom reprint requests should be addressed. E-mail: csurh{at}scripps.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

γc,

common γ chain;

LN,

lymph node;

LO,

lymphoid organ;

TSLP,

thymic stromal lymphopoietic;

CFSE,

5,6-carboxyfluorescein diacetate succinimidyl ester;

PE,

phosphatidylethanolamine