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 SIV-specific 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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/626600 |
| Date | 23 January 2018 |
| Creators | Webb, Gabriela M, Li, Shengbin, Mwakalundwa, Gwantwa, Folkvord, Joy M, Greene, Justin M, Reed, Jason S, Stanton, Jeffery J, Legasse, Alfred W, Hobbs, Theodore, Martin, Lauren D, Park, Byung S, Whitney, James B, Jeng, Emily K, Wong, Hing C, Nixon, Douglas F, Jones, R Brad, Connick, Elizabeth, Skinner, Pamela J, Sacha, Jonah B |
| Contributors | Univ Arizona, Div Infect Dis |
| Publisher | AMER SOC HEMATOLOGY |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2018 by The American Society of Hematology |
| Relation | http://www.bloodadvances.org/content/2/2/76/tab-article-info?sso-checked=true |
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