1. Cutting Edge: T Regulatory Cell Depletion Reactivates Latent Simian Immunodeficiency Virus (SIV) in Controller Macaques While Boosting SIV-Specific T Lymphocytes.
- Author
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He T, Brocca-Cofano E, Policicchio BB, Sivanandham R, Gautam R, Raehtz KD, Xu C, Pandrea I, and Apetrei C
- Subjects
- Animals, Antibodies, Viral blood, Antigens, Viral immunology, Cells, Cultured, Diphtheria Toxin administration & dosage, Humans, Immunity, Cellular, Interleukin-2 administration & dosage, Lymphocyte Activation, Lymphocyte Depletion, Macaca mulatta, RNA, Viral genetics, Recombinant Fusion Proteins administration & dosage, Viral Load drug effects, Virus Activation drug effects, Virus Replication drug effects, CD8-Positive T-Lymphocytes immunology, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus physiology, T-Lymphocytes, Regulatory immunology, Virus Latency drug effects
- Abstract
T regulatory cells (Tregs) are critical in shaping the latent HIV/SIV reservoir, as they are preferentially infected, reverse CD4
+ T cell activation status, and suppress CTL responses. To reactivate latent virus and boost cell-mediated immune responses, we performed in vivo Treg depletion with Ontak (denileukin diftitox) in two SIVsab-infected controller macaques. Ontak induced significant (>75%) Treg depletion and major CD4+ T cell activation, and only minimally depleted CD8+ T cells. The overall ability of Tregs to control immune responses was significantly impaired despite their incomplete depletion, resulting in both reactivation of latent virus (virus rebound to 103 viral RNA copies/ml plasma in the absence of antiretroviral therapy) and a significant boost of SIV-specific CD8+ T cell frequency, with rapid clearance of reactivated virus. As none of the latency-reversing agents in development have such dual activity, our strategy holds great promise for cure research., (Copyright © 2016 by The American Association of Immunologists, Inc.)- Published
- 2016
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