Understanding the role of interleukin-15 in T cell homeostasis and simian immunodeficiency virus pathogenesis

Interleukin-15 (IL-15) regulates NK cells and effector memory T cells (TEM), but its role in vivo and during simian immunodeficiency virus (SIV) infection remains unclear. Using rhesus macaques, we show that IL-15 is essential for NK cell maintenance and TEM stability; anti-IL-15 antibody caused NK cell depletion and induced high-turnover TEM homeostasis. During acute and chronic SIV infection, IL-15 neutralization did not alter viral replication or disease progression, despite significant immune cell changes. These findings indicate that elevated IL-15 during SIV infection is not a primary driver of pathogenesis and NK cells play a limited role in SIV control.