Distinct Cell Types Control Lymphoid Subset Development by Means of IL-15 and IL-15 Receptor Alpha Expression

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Apr 3

PMID 15060278

Citations 76

Authors

Kimberly S Schluns

Elizabeth C Nowak

Arturo Cabrera-Hernandez

Lynn Puddington

Leo Lefrancois

Hector L Aguila

Affiliations

Soon will be listed here.

Abstract

IL-15 and the IL-15 receptor (IL-15R)alpha 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-15R alpha 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-15R alpha expression by bone marrow-derived or parenchymal cells for mediating lymphocyte subset development. Naive CD8 T cell development required IL-15R alpha expression by both bone marrow-derived and parenchymal cells, whereas memory-phenotype CD8 T cells required IL-15R alpha expression only by hematopoietic cells. In contrast and surprisingly, the development of IEL subsets, particularly CD8 alpha alpha Thy1(-)V gamma 5(+) T cell antigen receptor gamma delta and the CD8 alpha alpha Thy1(-) T cell antigen receptor alpha beta IEL populations, depended completely on parenchymal cell expression of IL-15R alpha and IL-15 but not IL-15R beta. In the case of NK and NK/T cell generation and maturation, expression of IL-15 and IL-15R alpha 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.

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