Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor α expression

doi:10.1073/pnas.0307442101

Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor α expression

Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030

Edited by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO, and approved February 26, 2004 (received for review November 11, 2003)

Abstract

IL-15 and the IL-15 receptor (IL-15R)α chain are essential for normal development of naive CD8 T cells, intestinal intraepithelial lymphocytes (IEL), and natural killer (NK)/NK/T cells. However, whether IL-15Rα expression by these subsets is necessary for their production and which cell type needs to produce IL-15 to drive development are unknown. We analyzed the requirements for IL-15 and IL-15Rα expression by bone marrow-derived or parenchymal cells for mediating lymphocyte subset development. Naive CD8 T cell development required IL-15Rα expression by both bone marrow-derived and parenchymal cells, whereas memory-phenotype CD8 T cells required IL-15Rα expression only by hematopoietic cells. In contrast and surprisingly, the development of IEL subsets, particularly CD8ααThy1^–Vγ5⁺ T cell antigen receptor γδ and the CD8αα Thy1^– T cell antigen receptor αβ IEL populations, depended completely on parenchymal cell expression of IL-15Rα and IL-15 but not IL-15Rβ. In the case of NK and NK/T cell generation and maturation, expression of IL-15 and IL-15Rα by both parenchymal and hematopoietic cells was important, although the latter played the greatest role. These results demonstrated dichotomous mechanisms by which IL-15 regulated lymphoid development, interacting with distinct cell types depending on the developmental pathway.

Footnotes

↵ * To whom correspondence should be addressed. E-mail: aguila{at}nso1.uchc.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: IEL, intestinal intraepithelial lymphocyte; NK, natural killer; γC, common γ chain; BM, bone marrow; TCR, T cell antigen receptor; Wt, wild-type; IL-15R, IL-15 receptor; KO, knockout.