TY - JOUR
T1 - IL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa
AU - Cimbro, Raffaello
AU - Vassena, Lia
AU - Arthos, James
AU - Cicala, Claudia
AU - Kehrl, John H.
AU - Park, Chung
AU - Sereti, Irini
AU - Lederman, Michael M.
AU - Fauci, Anthony S.
AU - Lusso, Paolo
PY - 2012/9/27
Y1 - 2012/9/27
N2 - 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 guthoming 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-γnull (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.
AB - 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 guthoming 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-γnull (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.
UR - http://www.scopus.com/inward/record.url?scp=84866879225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866879225&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-06-434779
DO - 10.1182/blood-2012-06-434779
M3 - Article
C2 - 22896005
AN - SCOPUS:84866879225
VL - 120
SP - 2610
EP - 2619
JO - Blood
JF - Blood
SN - 0006-4971
IS - 13
ER -