Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma

被引：244

作者：

Hondowicz, Brian D. ^{[1
]}

An, Dowon ^{[2
]}

Schenkel, Jason M. ^{[3
]}

Kim, Karen S. ^{[1
]}

Steach, Holly R. ^{[1
]}

Krishnamurty, Akshay T. ^{[1
]}

Keitany, Gladys J. ^{[1
]}

Garza, Esteban N. ^{[1
]}

Fraser, Kathryn A. ^{[3
]}

Moon, James J. ^{[4
,5
,6
]}

Altemeier, William A. ^{[2
]}

Masopust, David ^{[3
]}

Pepper, Marion ^{[1
]}

机构：

[1] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98109 USA

[2] Univ Washington, Sch Med, Ctr Lung Biol, Seattle, WA 98109 USA

[3] Univ Minnesota, Sch Med, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USA

[4] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA

[5] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Charlestown, MA 02129 USA

[6] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

来源：

IMMUNITY | 2016年 / 44卷 / 01期

关键词：

DUST MITE ALLERGEN; FOLLICULAR HELPER-CELL; CD4(+) T-CELLS; TRANSCRIPTION FACTOR; LYMPHOCYTE EGRESS; TH2; CELLS; INFECTION; RESPONSES; PATTERNS; DIFFERENTIATION;

D O I：

10.1016/j.immuni.2015.11.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Exposure to inhaled allergens generates T helper 2 (Th2) CD4(+) T cells that contribute to episodes of inflammation associated with asthma. Little is known about allergen-specific Th2 memory cells and their contribution to airway inflammation. We generated reagents to understand how endogenous CD4(+) T cells specific for a house dust mite (HDM) allergen form and function. After allergen exposure, HDM-specific memory cells persisted as central memory cells in the lymphoid organs and tissue-resident memory cells in the lung. Experimental blockade of lymphocyte migration demonstrated that lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4(+) T cells. Investigation into the differentiation of pathogenic Trm cells revealed that interleukin-2 (IL-2) signaling was required for residency and directed a program of tissue homing migrational cues. These studies thus identify IL-2-dependent resident Th2 memory cells as drivers of lung allergic responses.

引用

页码：155 / 166

页数：12

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