Abstract
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 (T-FH) 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.
