IL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa.

TitleIL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa.
Publication TypeJournal Article
Year of Publication2012
AuthorsCimbro R, Vassena L, Arthos J, Cicala C, Kehrl JH, Park C, Sereti I, Lederman MM, Fauci AS, Lusso P
JournalBlood
Volume120
Issue13
Pagination2610-9
Date Published2012 Sep 27
ISSN1528-0020
KeywordsAdult, Animals, Blotting, Western, Cell Proliferation, Cytokines, Flow Cytometry, HIV Infections, HIV-1, Humans, Immunologic Memory, Integrins, Interleukin-7, Intestinal Mucosa, Lymphocyte Activation, Mice, Mice, Inbred NOD, Mice, SCID, Receptors, Interleukin-2, Signal Transduction, T-Lymphocytes
Abstract

Interleukin-7 (IL-7) is a nonredundant cytokine that plays a critical role in T-cell homeostasis and promotes immunologic reconstitution in lymphopenic hosts. Here, we show that IL-7, at doses that reflect suprahomeostatic concentrations achieved in lymphopenic hosts, is a potent and selective inducer of the gut-homing integrin α4β7 in human T cells, as documented both ex vivo and in vivo in patients enrolled in a clinical trial of IL-7 treatment. Induction of α4β7 by IL-7 occurs primarily in naive T cells and is associated with functional activation of the integrin, as indicated by increased binding activity for the specific α4β7 ligand, MAdCAM-1. The physiologic relevance of these findings was validated by the preferential homing of IL-7-treated naive human T cells to the intestinal compartment in humanized NOD/SCID/IL-2 receptor-γ(null) (NSG) mice. We also show that IL-7 triggers a peculiar activation program in naive T cells, characterized by the acquisition of memory-like phenotypic features and proliferation uncoupled from expression of classic T-cell activation markers. These findings provide a mechanism for the transient in vivo depletion of circulating T cells after IL-7 administration and suggest that intestinal homing and memory-like conversion of naive T cells are critical steps in the IL-7-driven immunologic reconstitution of lymphopenic hosts.

DOI10.1182/blood-2012-06-434779
Alternate JournalBlood
PubMed ID22896005
PubMed Central IDPMC3460683
Grant ListAI-068636 / AI / NIAID NIH HHS / United States
AI-069501 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States