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 Nagadenahalli 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

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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

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Lymphocyte Subsets
Macaca mulatta
Integrins
Mucous Membrane
Macaca
Inflammatory Bowel Diseases
B-Lymphocytes
Cell Count
T-Lymphocytes
Therapeutics
Immunoglobulin A
Acquired Immunodeficiency Syndrome
Lymphocytes
Inflammation
Infection
vedolizumab

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques. / Calenda, Giulia; Keawvichit, Rassamon; Arrode-Brusés, Géraldine; Pattanapanyasat, Kovit; Frank, Ines; Byrareddy, Siddappa Nagadenahalli; Arthos, James; Cicala, Claudia; Grasperge, Brooke; Blanchard, James L.; Gettie, Agegnehu; Reimann, Keith A.; Ansari, Aftab A.; Martinelli, Elena.

In: Journal of Immunology, Vol. 200, No. 2, 15.01.2018, p. 810-820.

Research output: Contribution to journalArticle

Calenda, G, Keawvichit, R, Arrode-Brusés, G, Pattanapanyasat, K, Frank, I, Byrareddy, SN, Arthos, J, Cicala, C, Grasperge, B, Blanchard, JL, Gettie, A, Reimann, KA, Ansari, AA & Martinelli, E 2018, 'Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques', Journal of Immunology, vol. 200, no. 2, pp. 810-820. https://doi.org/10.4049/jimmunol.1701150
Calenda, Giulia ; Keawvichit, Rassamon ; Arrode-Brusés, Géraldine ; Pattanapanyasat, Kovit ; Frank, Ines ; Byrareddy, Siddappa Nagadenahalli ; Arthos, James ; Cicala, Claudia ; Grasperge, Brooke ; Blanchard, James L. ; Gettie, Agegnehu ; Reimann, Keith A. ; Ansari, Aftab A. ; Martinelli, Elena. / Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques. In: Journal of Immunology. 2018 ; Vol. 200, No. 2. pp. 810-820.
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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.",
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T1 - Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques

AU - Calenda, Giulia

AU - Keawvichit, Rassamon

AU - Arrode-Brusés, Géraldine

AU - Pattanapanyasat, Kovit

AU - Frank, Ines

AU - Byrareddy, Siddappa Nagadenahalli

AU - Arthos, James

AU - Cicala, Claudia

AU - Grasperge, Brooke

AU - Blanchard, James L.

AU - Gettie, Agegnehu

AU - Reimann, Keith A.

AU - Ansari, Aftab A.

AU - Martinelli, Elena

PY - 2018/1/15

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N2 - 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.

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