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Author Notes:

Corresponding Author: Dr. Mirko Paiardini, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, 954 Gatewood Rd, Atlanta, GA 30329, mirko.paiardini@emory.edu Phone: 404-727-9840; Fax: 404-727-7768.

See publication for full list of author contributions.

We thank Stephanie Ehnert, Christopher Souder, Tracy Meeker, Kay Lee Summerville, Research Services, and all the animal care and veterinary staff at the Yerkes National Primate Research Center; Kiran Gill at the Emory University Flow Cytometry Core; and Thomas Vanderford, Benton Lawson, and Melon T. Nega at the Emory Center for AIDS Research (CFAR) Virology and Molecular Biomarkers Core.

We thank Nitasha Kumar for critical reading of the manuscript.

We also thank Cecily Midkiff of Tulane University, as well as Ann Mayne and Dawn Little of Emory University for technical assistance.

The SIVmac239 used to infect the RMs was kindly provided by Chris Miller. This work was supported by the NIAID, NIH under award numbers AI116379 and AI104278 (to M. Paiardini), ORIP/OD P51OD011132 (formerly NCRR P51RR000165, to the YNPRC), and P30AI50409 (to the Emory CFAR), as well as by amfAR 109109-57-RGRL (to M. Paiardini).

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

The authors have declared no conflict of interest exists.

Subjects:

Research Funding:

This work was supported by the NIAID, NIH under award numbers AI116379 and AI104278 (to M. Paiardini), ORIP/OD P51OD011132 (formerly NCRR P51RR000165, to the YNPRC), and P30AI50409 (to the Emory CFAR), as well as by amfAR 109109-57-RGRL (to M. Paiardini).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • IMMUNODEFICIENCY-VIRUS-INFECTION
  • GROWTH-FACTOR-BETA
  • HUMAN TH17 CELLS
  • CHRONIC HIV-INFECTION
  • GASTROINTESTINAL-TRACT
  • MUCOSAL IMMUNITY
  • T(H)17 CELLS
  • DENDRITIC CELLS
  • EXPRESSION
  • DEPLETION

The loss of CCR6(+) and CD161(+) CD4(+) T-cell homeostasis contributes to disease progression in SIV-infected rhesus macaques

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Journal Title:

Mucosal Immunology

Volume:

Volume 10, Number 4

Publisher:

, Pages 1082-1096

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Although previous studies have shown that CD4(+) T cells expressing CCR6 and CD161 are depleted from blood during HIV infection, the mechanisms underlying their loss remain unclear. In this study, we investigated how the homeostasis of CCR6(+) and CD161(+) CD4(+) T cells contributes to SIV disease progression and the mechanisms responsible for their loss from circulation. By comparing SIV infection in rhesus macaques (RMs) and natural host sooty mangabeys (SMs), we found that the loss of CCR6(+) and CD161(+) CD4(+) T cells from circulation is a distinguishing feature of progressive SIV infection in RMs. Furthermore, while viral infection critically contributes to the loss of CD161(+)CCR6(-)CD4(+) T cells, a redistribution of CCR6(+)CD161(-) and CCR6(+)CD161(+)CD4(+) T cells from the blood to the rectal mucosa is a chief mechanism for their loss during SIV infection. Finally, we provide evidence that the accumulation of CCR6(+)CD4(+) T cells in the mucosa is damaging to the host by demonstrating their reduction from this site following initiation of antiretroviral therapy in SIV-infected RMs and their lack of accumulation in SIV-infected SMs. These data emphasize the importance of maintaining CCR6(+) and CD161(+) CD4(+) T-cell homeostasis, particularly in the mucosa, to prevent disease progression during pathogenic HIV/SIV infection.

Copyright information:

Copyright © 2017, Rights Managed by Nature Publishing Group

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