A new Cell Reports study from the Ndhlovu Lab with partners in South Africa and Malawi explains how HIV survives in lymph nodes during treatment. The team shows that the virus weakens nearby “killer” CD8 T cells right where HIV concentrates most, inside B cell follicles.

Researchers examined lymph node tissue from people with and without HIV. Using advanced imaging and gene readouts in the tissue itself, they mapped where the virus and immune cells sit. They found that follicles with more HIV drew in more CD8 T cells, but many of these cells lacked granzyme B, a protein CD8 T cells need to kill infected targets.

These results point to a local brake on killer T cells. In follicles with more HIV, HLA-E levels are higher. HLA-E engages the NKG2A receptor on CD8 T cells and slows them down. These NKG2A-positive cells also have less granzyme B, a protein needed to kill infected cells. Together, this weakens killing right where HIV hides.

Lymph node follicles are a key refuge for HIV during therapy. Because drugs that block the HLA-E or NKG2A pathway are already in development for cancer, this work suggests a practical way to test whether lifting this brake could re-energize immune attack on HIV in tissues.