@article{679d809de95649e9bbdc9907ec065c9d,
title = "Early treatment of SIV+ macaques with an α 4 β 7 mAb alters virus distribution and preserves CD4 + T cells in later stages of infection",
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.",
author = "Santangelo, {P. J.} and C. Cicala and Byrareddy, {S. N.} and Ortiz, {K. T.} and D. Little and Lindsay, {K. E.} and S. Gumber and Hong, {J. J.} and K. Jelicic and Rogers, {K. A.} and C. Zurla and F. Villinger and Ansari, {A. A.} and Fauci, {A. S.} and J. Arthos",
note = "Funding Information: Primate Reagents Resource supported by AI126683 and Funding Information: 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 co-ordinating 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 a4b7 mAb, the normal recombinant rhesus IgG and the anti-CD4 (Fab)2. We are also grateful to E. Husband and his colleagues at the Emory hospital imaging facility for scanning the animals, Drs. S. Jean, J. Wood, F Connor-Stroud and the Yerkes Veterinary and animal care team for their support of these studies. Finally, we are grateful to Alia Sajani for editorial assistance, and A. Weddle for preparation of graphics. 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 F.V. Anti a4b7 mAb, rhesus IgG mAb and anti-CD4 (Fab)2 provided by the NIH Publisher Copyright: {\textcopyright} The Author(s) 2018.",
year = "2018",
month = may,
day = "1",
doi = "10.1038/mi.2017.112",
language = "English (US)",
volume = "11",
pages = "932--946",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Elsevier B.V.",
number = "3",
}