Giulia CalendaRassamon KeawvichitGéraldine Arrode-BrusésKovit PattanapanyasatInes FrankSiddappa N. ByrareddyJames ArthosClaudia CicalaBrooke GraspergeJames L. BlanchardAgegnehu GettieKeith A. ReimannAftab A. AnsariElena MartinelliTulane National Primate Research CenterRockefeller UniversityPopulation Council HeadquartersNational Institute of Allergy and Infectious DiseasesUniversity of Nebraska Medical CenterFaculty of Medicine, Siriraj Hospital, Mahidol UniversityEmory University School of MedicineUniversity of Massachusetts Medical School2019-08-232019-08-232018-01-15Journal of Immunology. Vol.200, No.2 (2018), 810-82015506606002217672-s2.0-85044748819https://repository.li.mahidol.ac.th/handle/20.500.14594/46055Copyright © 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.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.4049/jimmunol.1701150