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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.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Dec 15; Vol. 197 (12), pp. 4535-4539. Date of Electronic Publication: 2016 Nov 11. - Publication Year :
- 2016
-
Abstract
- T regulatory cells (Tregs) are critical in shaping the latent HIV/SIV reservoir, as they are preferentially infected, reverse CD4 <superscript>+</superscript> 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 <superscript>+</superscript> T cell activation, and only minimally depleted CD8 <superscript>+</superscript> 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 <superscript>3</superscript> viral RNA copies/ml plasma in the absence of antiretroviral therapy) and a significant boost of SIV-specific CD8 <superscript>+</superscript> 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.<br /> (Copyright © 2016 by The American Association of Immunologists, Inc.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 197
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 27837106
- Full Text :
- https://doi.org/10.4049/jimmunol.1601539