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
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
收藏
页码:1397 / 1400
页数:4
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