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Cutting Edge: T Regulatory Cell Depletion Reactivates Latent Simian Immunodeficiency Virus (SIV) in Controller Macaques While Boosting SIV-Specific T Lymphocytes.

Cutting Edge: T Regulatory Cell Depletion Reactivates Latent Simian Immunodeficiency Virus (SIV) in Controller Macaques While Boosting SIV-Specific T Lymphocytes.
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He T, Brocca-Cofano E, Policicchio BB, Sivanandham R, Gautam R, Raehtz KD, Xu C, Pandrea I, Apetrei C,


He T, Brocca-Cofano E, Policicchio BB, Sivanandham R, Gautam R, Raehtz KD, Xu C, Pandrea I, Apetrei C, (click to view)

He T, Brocca-Cofano E, Policicchio BB, Sivanandham R, Gautam R, Raehtz KD, Xu C, Pandrea I, Apetrei C,

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Journal of immunology (Baltimore, Md. : 1950) 2016 11 11197(12) 4535-4539

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 10(3) 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.

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