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

ABSTRACT

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

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 registration: ClinicalTrials.gov NCT02452268