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

Giulia Calenda, Rassamon Keawvichit, Géraldine Arrode-Brusés, Kovit Pattanapanyasat, Ines Frank, Siddappa N. Byrareddy, James Arthos, Claudia Cicala, Brooke Grasperge, James L. Blanchard, Agegnehu Gettie, Keith A. Reimann, Aftab A. Ansari, Elena Martinelli

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)810-820
Number of pages11
JournalJournal of Immunology
Volume200
Issue number2
DOIs
StatePublished - Jan 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Integrin α<sub>4</sub>β<sub>7</sub> Blockade Preferentially Impacts CCR6<sup>+</sup> Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques'. Together they form a unique fingerprint.

  • Cite this

    Calenda, G., Keawvichit, R., Arrode-Brusés, G., Pattanapanyasat, K., Frank, I., Byrareddy, S. N., Arthos, J., Cicala, C., Grasperge, B., Blanchard, J. L., Gettie, A., Reimann, K. A., Ansari, A. A., & Martinelli, E. (2018). Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques. Journal of Immunology, 200(2), 810-820. https://doi.org/10.4049/jimmunol.1701150