Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals

• DOI: 10.1126/scitranslmed.aau4711
• Publication Date: 2018-10-03T18:10:47Z
• Authors: Mathieu Uzzan; Minami Tokuyama; Adam K. Rosenstein; Costin Tomescu; Ivo N. SahBandar; Huaibin M. Ko; Louise Leyre; Anupa Chokola; Emma Kaplan-Lewis; Gabriela Rodriguez; Akihiro Seki; Michael J. Corley; Judith Aberg; Annalena La Porte; Eun-young Park; Hideki Ueno; Ioannis Oikonomou; Itai Doron; Iliyan D. Iliev; Benjamin K. Chen; Jennifer Lui; Timothy W. Schacker; Glaucia C. Furtado; Sergio A. Lira; Jean-Frederic Col...; Amir Horowitz; Jean K. Lim; Nicolas Chomont; Adeeb H. Rahman; Luis J. Montaner; Lishomwa C. Ndhlovu; Saurabh Mehandru
• Keywords: Simian immunodeficiency virus; Homing (biology)

Gut homing CD4+ T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating disease course of simian immunodeficiency virus nonhuman primate studies, mechanisms drug action remain elusive. We present a cohort individuals mild inflammatory bowel concomitant infection receiving treatment. By sampling immune inductive effector sites GI tract, we discovered that therapy led significant unexpected attenuation lymphoid aggregates, most notably terminal ileum. Given aggregates serve as important sanctuary for maintaining reservoirs, their attrition has implications therapeutics eradication efforts defines rational basis use infection.