Integrin α 4 β 7 Blockade Preferentially Impacts CCR6 + Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques

J Immunol. 2018 Jan 15;200(2):810-820. doi: 10.4049/jimmunol.1701150. Epub 2017 Dec 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Integrins / antagonists & inhibitors*
  • Lymphocyte Count*
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism*
  • Macaca mulatta
  • Mucous Membrane / immunology*
  • Mucous Membrane / metabolism*
  • Organ Specificity / immunology
  • Receptors, CCR6 / metabolism*


  • Integrins
  • Receptors, CCR6
  • integrin alpha4beta7