A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells

被引：298

作者：

Stary, Georg ^{[1
]}

Olive, Andrew ^{[1
]}

Radovic-Moreno, Aleksandar F. ^{[2
,3
]}

Gondek, David ^{[1
]}

Alvarez, David ^{[1
]}

Basto, Pamela A. ^{[2
,3
]}

Perro, Mario ^{[1
]}

Vrbanac, Vladimir D. ^{[4
]}

Tager, Andrew M. ^{[4
]}

Shi, Jinjun ^{[6
]}

Yethon, Jeremy A. ^{[5
]}

Farokhzad, Omid C. ^{[6
,7
]}

Langer, Robert ^{[2
,3
]}

Starnbach, Michael N. ^{[1
]}

von Andrian, Ulrich H. ^{[1
,8
]}

机构：

[1] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA

[2] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[3] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[5] Sanofi Pasteur, Cambridge, MA 02139 USA

[6] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA

[7] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia

[8] MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA

来源：

SCIENCE | 2015年 / 348卷 / 6241期

基金：

美国国家科学基金会;

关键词：

CD103(+) DENDRITIC CELLS; RESIDENT MEMORY; FIELD TRIAL; MEDIATED PROTECTION; IMMUNE-RESPONSES; ORAL TOLERANCE; INFECTION; MIGRATION; EFFECTOR; ANTIGEN;

D O I：

10.1126/science.aaa8205

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-g-producing CD4 T cells. By contrast, we report that mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-) dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b(-)CD103(+) DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T cells, but only mucosal vaccination induced effector T cells that rapidly seeded uterine mucosa with resident memory T cells (T-RM cells). Optimal Ct clearance required both TRM seeding and subsequent infection-induced recruitment of circulating memory T cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T cell subsets with distinct migratory properties.

引用

页数：15

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