The BLT Humanized Mouse Model as a Tool for Studying Human Gamma Delta T Cell-HIV Interactions In Vivo

Gamma-delta (gamma delta) T cells recognize antigens in a major histocompatibility complex (MHC) independent and have cytotoxic capability. Human immunodeficiency virus (HIV) infection reduces the proportion of the V delta 2 cell subset compared to the V delta 1 cell subset of gamma delta T cells in the blood in most infected individuals, except for elite controllers. The capacity of V delta 2 T cells to kill HIV-infected targets has been demonstrated in vitro, albeit in vivo confirmatory studies are lacking. Here, we provide the first characterization of gamma delta T cell-HIV interactions in bone marrow-liver-thymus (BLT) humanized mice and examined the immunotherapeutic potential of V delta 2 T cells in controlling HIV replication in vivo. We demonstrate a reduced proportion of V delta 2 T cells and an increased proportion of V delta 1 T cells in HIV-infected BLT humanized mice, like in HIV-positive individuals. HIV infection in BLT humanized mice also impaired the ex vivo expansion of V delta 2 T cells, like in HIV-positive individuals. Adoptive transfer of activated V delta 2 T cells did not control HIV replication during cell-associated HIV transmission in BLT humanized mice but instead exacerbated viremia, suggesting that V delta 2 T cells may serve as early targets for HIV replication. Our findings demonstrate that BLT humanized mice can model gamma delta T cell-HIV interactions in vivo.

Automated summary

This study characterizes the interactions between gamma-delta T cells and HIV in a mouse model and explores the immunotherapeutic potential of V delta 2 T cells in controlling HIV replication. The findings reveal that HIV infection affects the proportion and ex vivo expansion of V delta 2 T cells in BLT humanized mice, and the adoptive transfer of activated V delta 2 T cells does not control HIV replication but exacerbates viremia.