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Author Notes:

To whom correspondence should be addressed: Dr. Philip J. Santangelo Georgia Institute of Technology, 225 North Ave NW, Atlanta, GA, 30332; philip.santangelo@bme.gatech.edu and Dr. James Arthos, Laboratory of Immunoregulation, Bldg. 10, Room 6A08, NIH, 9000 Rockville, MD 20892; jarthos@niaid.nih.gov

P J Santangelo, C Cicala & S N Byrareddy; these authors contributed equally to this work.

The nonhuman primate studies were designed and overseen by JA, CC, FV and AAA.

The laboratory-based studies were conducted by SNB, JJH, KER, and SG with technical assistance by KO and DL.

See publication for full list of author contributions.

The authors are grateful to the veterinary staff of the Yerkes National Primate Research Center of Emory University specially Ms. Stephanie Ehnert and her supporting staff members for coordinating all the nonhuman primate work.

In addition, the authors are grateful to Dr. D. M. Schuster and the technical staff of the Department of Imaging Sciences and Radiology of Emory University Hospital, Emory University School of Medicine for their help and guidance for the imaging studies.

The authors also would like to thank Dr. James Hoxie for the provision of the 7D3 hybridoma, Dr. K. Reimann and Mr. Adam Busby for the provision of primatized α4β7 mAb, the normal recombinant rhesus IgG and the anti-CD4 (Fab)2.

See publication for full list of acknowledgements.

Disclosure: The authors declared no conflict of interest.

Subjects:

Research Funding:

This work is supported by NIH R01 AI098628 to A. A. A., the Intramural Research Program, NIAID, NIH, Bethesda, MD and NIH R01 AI111907 to P.J.S and FV. Anti α4β7 mAb, rhesus IgG mAb and anti-CD4 (Fab)2 provided by the NIH Nonhuman Primate Reagents Resource supported by AI126683 and OD010976.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • SIMIAN IMMUNODEFICIENCY VIRUS
  • VASCULAR ADDRESSIN MADCAM-1
  • INFLAMMATORY LIVER-DISEASE
  • ANTIRETROVIRAL THERAPY
  • LYMPHOID-TISSUE
  • INTEGRIN ALPHA(4)BETA(7)
  • GASTROINTESTINAL-TRACT
  • RHESUS MACAQUES
  • CHLAMYDIA-TRACHOMATIS
  • MAINTENANCE THERAPY

Early treatment of SIV plus macaques with an alpha(4)beta(7) mAb alters virus distribution and preserves CD4(+) T cells in later stages of infection

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Journal Title:

Mucosal Immunology

Volume:

Volume 11, Number 3

Publisher:

, Pages 932-946

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Integrin α 4 β 7 mediates the trafficking of leukocytes, including CD4 + T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α 4 β 7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4 + cells in rhesus macaques infected with SIV. We determined that α 4 β 7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes. These sites are not directly linked to α 4 β 7 mediated homing; however, the most pronounced reduction in viral load was observed in the colon. Despite this reduction, α 4 β 7 mAb treatment did not prevent an apparent depletion of CD4 + T cells in gut in the acute phase of infection that is characteristic of HIV/SIV infection. However, α 4 β 7 mAb appeared to facilitate the preservation or restoration of CD4 + T cells in gut tissues at later stages of infection. Since damage to the gut is believed to play a central role in HIV pathogenesis, these results support further evaluation of α 4 β 7 antagonists in the study and treatment of HIV disease.

Copyright information:

© The Author(s) 2018.

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