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Title: Integrin α<inf>4</inf>β<inf>7</inf> Blockade Preferentially Impacts CCR6<sup>+</sup> Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques
Authors: Giulia Calenda
Rassamon Keawvichit
Géraldine Arrode-Brusés
Kovit Pattanapanyasat
Ines Frank
Siddappa N. Byrareddy
James Arthos
Claudia Cicala
Brooke Grasperge
James L. Blanchard
Agegnehu Gettie
Keith A. Reimann
Aftab A. Ansari
Elena Martinelli
Tulane National Primate Research Center
Rockefeller University
Population Council Headquarters
National Institute of Allergy and Infectious Diseases
University of Nebraska Medical Center
Faculty of Medicine, Siriraj Hospital, Mahidol University
Emory University School of Medicine
University of Massachusetts Medical School
Keywords: Immunology and Microbiology;Medicine
Issue Date: 15-Jan-2018
Citation: Journal of Immunology. Vol.200, No.2 (2018), 810-820
Abstract: Copyright © 2018 by The American Association of Immunologists, Inc. Infusion of a simianized anti-α4β7 mAb (Rh-α4β7) just before and following SIV infection protected rhesus macaques from developing AIDS and partially from vaginal SIV acquisition. Recently, short-term treatment with Rh-α4β7 in combination with cART was found to lead to prolonged viral suppression after withdrawal of all therapeutic interventions. The humanized form of Rh-α4β7, vedolizumab, is a highly effective treatment for inflammatory bowel disease. To clarify the mechanism of action of Rh-α4β7, naive macaques were infused with Rh-α4β7 and sampled in blood and tissues before and after treatment to monitor several immune cell subsets. In blood, Rh-α4β7 increased the CD4+ and CD8+ T cell counts, but not B cell counts, and preferentially increased CCR6+ subsets while decreasing CD103+ and CD69+ lymphocytes. In mucosal tissues, surprisingly, Rh-α4β7 did not impact integrin α4+ cells, but decreased the frequencies of CCR6+ and CD69+ CD4+ T cells and, in the gut, Rh-α4β7 transiently decreased the frequency of memory and IgA+ B cells. In summary, even in the absence of inflammation, Rh-α4β7 impacted selected immune cell subsets in different tissues. These data provide new insights into the mechanisms by which Rh-α4β7 may mediate its effect in SIV-infected macaques with implications for understanding the effect of treatment with vedolizumab in patients with inflammatory bowel disease.
ISSN: 15506606
Appears in Collections:Scopus 2018

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