Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection

被引：115

作者：

Byrareddy, Siddappa N. ^{[1
]}

Kallam, Brianne ^{[1
]}

Arthos, James ^{[2
]}

Cicala, Claudia ^{[2
]}

Nawaz, Fatima ^{[2
]}

Hiatt, Joseph ^{[2
]}

Kersh, Ellen N. ^{[3
]}

McNicholl, Janet M. ^{[3
]}

Hanson, Debra ^{[3
]}

Reimann, Keith A. ^{[4
]}

Brameier, Markus ^{[5
]}

Walter, Lutz ^{[5
]}

Rogers, Kenneth ^{[6
]}

Mayne, Ann E. ^{[1
]}

Dunbar, Paul ^{[1
]}

Villinger, Tara ^{[1
]}

Little, Dawn ^{[1
]}

Parslow, Tristram G. ^{[1
]}

Santangelo, Philip J. ^{[7
,8
]}

Villinger, Francois ^{[1
,6
]}

Fauci, Anthony S. ^{[2
]}

Ansari, Aftab A. ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

[2] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[3] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA

[4] Univ Massachusetts, Sch Med, Mass Biol, Boston, MA 02125 USA

[5] German Primate Ctr, Leibniz Inst Primate Res, Primate Genet Lab, Gottingen, Germany

[6] Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA

[7] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA

[8] Emory Univ, Atlanta, GA 30322 USA

来源：

NATURE MEDICINE | 2014年 / 20卷 / 12期

关键词：

T-CELL SUBSET; MAINTENANCE THERAPY; IMMUNE ACTIVATION; ALPHA-4-BETA-7; VEDOLIZUMAB; INDUCTION; DEPLETION; RECEPTOR; TRACT; CD4;

D O I：

10.1038/nm.3715

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

alpha(4)beta(7) integrin expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-alpha(4)beta(7) monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting alpha(4)beta(7) reduces mucosal transmission of Sly in macaques.

引用

页码：1397 / 1400

页数：4

共 20 条

[11] Identification of homing receptors that mediate the recruitment of CD4 T cells to the genital tract following intravaginal infection with Chlamydia trachomatis [J].

Kelly, KA ;

Rank, RG .

INFECTION AND IMMUNITY, 1997, 65 (12) :5198-5208

[12] Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques [J].

Kwa, Suefen ;

Kannanganat, Sunil ;

Nigam, Pragati ;

Siddiqui, Mariam ;

Shetty, Ravi Dyavar ;

Armstrong, Wendy ;

Ansari, Aftab ;

Bosinger, Steven E. ;

Silvestri, Guido ;

Amara, Rama Rao .

BLOOD, 2011, 118 (10) :2763-2773

[13]

Martinelli E, 2013, JAIDS-J ACQ IMM DEF, V64, P325, DOI 10.1097/QAI.0b013e31829f6e1a

[14] Characterization of a Human Cervical CD4+ T Cell Subset Coexpressing Multiple Markers of HIV Susceptibility [J].

McKinnon, Lyle R. ;

Nyanga, Billy ;

Chege, Duncan ;

Izulla, Preston ;

Kimani, Makobu ;

Huibner, Sanja ;

Gelmon, Lawrence ;

Block, Katharine E. ;

Cicala, Claudia ;

Anzala, A. Omu ;

Arthos, James ;

Kimani, Joshua ;

Kaul, Rupert .

JOURNAL OF IMMUNOLOGY, 2011, 187 (11) :6032-6042

[15] Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract [J].

Mehandru, S ;

Poles, MA ;

Tenner-Racz, K ;

Horowitz, A ;

Hurley, A ;

Hogan, C ;

Boden, D ;

Racz, P ;

Markowitz, M .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (06) :761-770

[16] Monoclonal Antibodies to the V2 Domain of MN-rgp120: Fine Mapping of Epitopes and Inhibition of α4β7 Binding [J].

Nakamura, Gerald R. ;

Fonseca, Dora P. A. J. ;

O'Rourke, Sara M. ;

Vollrath, Aaron L. ;

Berman, Phillip W. .

PLOS ONE, 2012, 7 (06)

[17] The Genotype of Early-Transmitting HIV gp120s Promotes α4β7 -Reactivity, Revealing α4β7+/CD4+ T cells As Key Targets in Mucosal Transmission [J].

Nawaz, Fatima ;

Cicala, Claudia ;

Van Ryk, Donald ;

Block, Katharine E. ;

Jelicic, Katija ;

McNally, Jonathan P. ;

Ogundare, Olajumoke ;

Pascuccio, Massimiliano ;

Patel, Nikita ;

Wei, Danlan ;

Fauci, Anthony S. ;

Arthos, James .

PLOS PATHOGENS, 2011, 7 (02)

[18] Preliminary in vivo efficacy studies of a recombinant rhesus anti-α4β7 monoclonal antibody [J].

Pereira, L. E. ;

Onlamoon, N. ;

Wang, X. ;

Wang, R. ;

Li, J. ;

Reimann, K. A. ;

Villinger, F. ;

Pattanapanyasat, K. ;

Mori, K. ;

Ansari, A. A. .

CELLULAR IMMUNOLOGY, 2009, 259 (02) :165-176

[19] Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease [J].

Sandborn, William J. ;

Feagan, Brian G. ;

Rutgeerts, Paul ;

Hanauer, Stephen ;

Colombel, Jean-Frederic ;

Sands, Bruce E. ;

Lukas, Milan ;

Fedorak, Richard N. ;

Lee, Scott ;

Bressler, Brian ;

Fox, Irving ;

Rosario, Maria ;

Sankoh, Serap ;

Xu, Jing ;

Stephens, Kristin ;

Milch, Catherine ;

Parikh, Asit .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (08) :711-721

[20] Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection [J].

Veazey, RS ;

DeMaria, M ;

Chalifoux, LV ;

Shvetz, DE ;

Pauley, DR ;

Knight, HL ;

Rosenzweig, M ;

Johnson, RP ;

Desrosiers, RC ;

Lackner, AA .

SCIENCE, 1998, 280 (5362) :427-431

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