Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent
human immunodeficiency virus infection is an early regulatory T (
Treg)
cell response that blunts virus-specific responses. Using the
simian immunodeficiency virus (SIV)-infected rhesus macaque model, we show that, indeed,
viral replication and
immune activation in
lymphatic tissue drive a premature
immunosuppressive response, with dramatic increases in the
frequencies of
CD4+
CD25+
FOXP3+
Treg cells, transforming growth factor- beta 1+ cells, interleukin-10+ cells, and
indoleamine 2,3-dioxygenase+CD3+ cells. When we compared SIV
infection with rhesus
cytomegalovirus (RhCMV)
infection, we found that the
frequency of
Treg cells paralleled the magnitude of
immune activation during both
infections but that the magnitude of
immune activation and of the
Treg cell response were lower and peaked much later during RhCMV
infection. Importantly, the
frequency of
Treg cells inversely
correlated with the magnitude of the SIV-specific
cytotoxic T lymphocyte response. We conclude that an early
Treg cell response during acute SIV
infection may contribute to viral persistence by prematurely limiting the
antiviral immune response before
infection is cleared.
