Integrin α 4 β 7 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 macaques from developing AIDS and 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 macaques were 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 macaques with implications for understanding the effect of treatment with vedolizumab in patients with inflammatory bowel disease.
(Copyright © 2018 by The American Association of Immunologists, Inc.)