The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles

被引：60

作者：

Webb, Gabriela M. ^{[1
,2
]}

Li, Shengbin ^{[3
]}

Mwakalundwa, Gwantwa ^{[3
]}

Folkvord, Joy M. ^{[4
]}

Greene, Justin M. ^{[1
,2
]}

Reed, Jason S. ^{[1
,2
]}

Stanton, Jeffery J. ^{[2
]}

Legasse, Alfred W. ^{[2
]}

Hobbs, Theodore ^{[2
]}

Martin, Lauren D. ^{[2
]}

Park, Byung S. ^{[2
]}

Whitney, James B. ^{[5
,6
]}

Jeng, Emily K. ^{[7
]}

Wong, Hing C. ^{[7
]}

Nixon, Douglas F. ^{[8
]}

Jones, R. Brad ^{[8
]}

Connick, Elizabeth ^{[4
]}

Skinner, Pamela J. ^{[3
]}

Sacha, Jonah B. ^{[1
,2
]}

机构：

[1] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA

[2] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR 97201 USA

[3] Univ Minnesota, Dept Vet Biomed Sci, St Paul, MN 55108 USA

[4] Univ Arizona, Div Infect Dis, Tucson, AZ USA

[5] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA USA

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

[7] Altor BioSci Corp, Miramar, FL USA

[8] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA

来源：

BLOOD ADVANCES | 2018年 / 2卷 / 02期

基金：

美国国家卫生研究院;

关键词：

NONHUMAN-PRIMATES; VIRAL-INFECTION; FUSION COMPLEX; REPLICATION; THERAPY; TISSUES; HIV; CTL; NK;

D O I：

10.1182/bloodadvances.2017012971

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Sequestering of latent HIV in follicular helper T cells within B-cell follicles that largely exclude cytotoxic T cells is a major barrier to cellular immune-based approaches to eradicate HIV. Here, we show that the clinical-grade human interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian immunodeficiency virus (SIV) specific CD8(+) T cells from the peripheral blood into B-cell follicles. In agreement with the increased trafficking of SIVspecific cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite controlling macaques contained fewer cells expressing SIV RNA or harboring SIV DNA post ALT-803 treatment. These data establish ALT-803 as an immunotherapeutic for HIV and other chronic viral pathogens that evade host immunity by persisting in B-cell follicles.

引用

页码：76 / 84

页数：9

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