PLoS Pathogens (Feb 2018)

Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes.

  • Dionysios C Watson,
  • Eirini Moysi,
  • Antonio Valentin,
  • Cristina Bergamaschi,
  • Santhi Devasundaram,
  • Sotirios P Fortis,
  • Jenifer Bear,
  • Elena Chertova,
  • Julian Bess,
  • Ray Sowder,
  • David J Venzon,
  • Claire Deleage,
  • Jacob D Estes,
  • Jeffrey D Lifson,
  • Constantinos Petrovas,
  • Barbara K Felber,
  • George N Pavlakis

DOI
https://doi.org/10.1371/journal.ppat.1006902
Journal volume & issue
Vol. 14, no. 2
p. e1006902

Abstract

Read online

B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN. Following hetIL-15 treatment, multiplexed quantitative image analysis (histo-cytometry) of LN revealed increased numbers of granzyme B+ T cells in B cell follicles and SHIV RNA was decreased in plasma and in LN. Based on these properties, hetIL-15 shows promise as a potential component in combination immunotherapy regimens to target AIDS virus sanctuaries and reduce long-term viral reservoirs in HIV-1 infected individuals.Trial registrationClinicalTrials.gov NCT02452268.