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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Bibliographische Detailangaben
Zeitschriftentitel:	The Journal of Immunology
Personen und Körperschaften:	He, Tianyu, Brocca-Cofano, Egidio, Policicchio, Benjamin B., Sivanandham, Ranjit, Gautam, Rajeev, Raehtz, Kevin D., Xu, Cuiling, Pandrea, Ivona, Apetrei, Cristian
In:	The Journal of Immunology, 197, 2016, 12, S. 4535-4539
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	The American Association of Immunologists
Schlagwörter:	Immunology Immunology and Allergy

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Zusammenfassung:	<jats:title>Abstract</jats:title> <jats:p>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 (&gt;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.</jats:p>
Umfang:	4535-4539
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.1601539