The Lymphopenic Environment of CD132 (Common γ-Chain)-Deficient Hosts Elicits Rapid Homeostatic Proliferation of Naive T Cells via IL-15

Abstract

Homeostatic proliferation for naive T cells is observed readily only under lymphopenic conditions in response to elevated levels of IL-7 and contact with self-MHC/peptide ligands. Homeostatic proliferation occurs at a slow pace and gradually induces the dividing cells to acquire characteristics of memory cells. We describe a novel type of homeostatic proliferation whereby naive T cells proliferate at a significantly faster rate, resembling the proliferation speed induced by foreign Ags, and the expanding cells rapidly differentiate into central memory cells. Remarkably, such rapid homeostatic proliferation is driven by a combination of IL-2 and IL-15, with IL-15 playing a bigger role, and applies for a wide repertoire of CD8(+) naive T cells, including many TCR-transgenic lines, even those that fail to undergo IL-7-driven homeostatic proliferation. Thus, naive T cells can be induced to undergo homeostatic proliferation of variable speed with a few members of the common gamma-chain (CD132) family of cytokines, the speed of proliferation depending on the levels of the particular cytokine involved.