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

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