Preliminary in vivo efficacy studies of a recombinant rhesus anti-α4β7 monoclonal antibody

被引：23

作者：

Pereira, L. E. ^{[1
]}

Onlamoon, N. ^{[1
]}

Wang, X. ^{[2
]}

Wang, R. ^{[2
]}

Li, J. ^{[2
]}

Reimann, K. A. ^{[2
]}

Villinger, F. ^{[1
]}

Pattanapanyasat, K. ^{[3
]}

Mori, K. ^{[4
]}

Ansari, A. A. ^{[1
]}

机构：

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

[2] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA

[3] Mahidol Univ, Fac Med, Dept Immunol, Off Res & Dev,Siriraj Hosp, Bangkok 10700, Thailand

[4] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo 1628640, Japan

来源：

CELLULAR IMMUNOLOGY | 2009年 / 259卷 / 02期

关键词：

Cell trafficking; Antibodies; AIDS; T-cells; Rhesus macaque; Act1; Alpha4beta7; integrin; SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL DEPLETION; INTEGRIN ALPHA-4-BETA-7; GASTROINTESTINAL-TRACT; HUMANIZED ANTIBODY; SOOTY MANGABEYS; DENDRITIC CELLS; LYMPHOID-TISSUE; HOST RESPONSES; INFECTION;

D O I：

10.1016/j.cellimm.2009.06.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Recent findings established that primary targets of HIV/SIV are lymphoid cells within the gastrointestinal (GI) tract. Focus has therefore shifted to T-cells expressing alpha(4)beta(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha(4)beta(7)+ T-cells in HIV/SIV pathogenesis include their depletion or blockade of their synthesis, binding and/or homing capabilities in vivo. Such studies can ideally be conducted in rhesus macaques (RM), the non-human primate model of AIDS. Characterization of alpha(4)beta(7) expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naive and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. intravenous administration of a single 50 mg/kg dose of recombinant rhesus alpha(4)beta(7) antibody resulted in significant initial decline of alpha(4)beta(7)+ lymphocytes and sustained coating of the alpha(4)beta(7) receptor in both the periphery and GI tissues. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：165 / 176

页数：12

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