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

Cimbro, Raffaello, Vassena, Lia, Arthos, James, Cicala, Claudia, Kehrl, John H., Park, Chung, Sereti, Irini, Lederman, Michael M., Fauci, Anthony S., Lusso, Paolo·2012·Blood
DOI 10.1182/blood-2012-06-434779
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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-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.

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Metadata

Authors
Cimbro, R., Vassena, L., Arthos, J., Cicala, C., Kehrl, J. H., Park, C., Sereti, I., Lederman, M. M., Fauci, A. S., & Lusso, P.
Affiliations
  • Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and
  • Center for AIDS Research, Case-Western Reserve University, University Hospitals of Cleveland, Cleveland, OH
Venue
Blood
Publisher
American Society of Hematology
Published
2012-09-27
Volume
120
Issue
13
Pages
2610-2619
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2012-06-434779
Cited by
94
References
1
Language
en

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