Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques

Infusion of a simianized anti-α 4 β 7 mAb (Rh-α 4 β 7 ) just before and following SIV infection protected rhesus macaquesfrom developing AIDSand partially from vaginal SIV acquisition. Recently, short-term treatment with Rh-α 4 β 7 in combination with cART was found to lead to prolonged viral suppression after withdrawal of all therapeutic interventions. The humanized form of Rh-α 4 β 7 , vedolizumab, is a highly effective treatment for inflammatory bowel disease. To clarify the mechanism of action of Rh-α 4 β 7 , naive macaqueswere infused with Rh-α 4 β 7 and sampled in blood and tissues before and after treatment to monitor several immune cell subsets. In blood, Rh-α 4 β 7 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-α 4 β 7 did not impact integrin α 4 + cells, but decreased the frequencies of CCR6 + and CD69+ CD4 + T cells and, in the gut, Rh-α 4 β 7 transiently decreased the frequency of memory and IgA + B cells. In summary, even in the absence of inflammation, Rh-α 4 β 7 impacted selected immune cell subsets in different tissues. These data provide new insights into the mechanisms by which Rh-α 4 β 7 may mediate its effect in SIV-infected macaqueswith implications for understanding the effect of treatment with vedolizumabin patients with inflammatory bowel disease.