Depletion and dysfunction of Vγ2Vδ2 T cells in HIV disease: mechanisms, impacts and therapeutic implications

Infection with human immunodeficiency virus (HIV) disrupts the balance among gamma delta T cell subsets, with increasing V delta 1 + cells and substantial depletion of circulating V delta 2+ cells. Depletion is an indirect effect of HIV in CD4-negative V delta 2 cells, but is specific for phosphoantigen-responsive subpopulations identified by the V gamma 2-J gamma 1.2 (also called V gamma 9-J gamma P) T cell receptor rearrangement. The extent of cell loss and recovery is related closely to clinical status, with highest levels of functional V delta 2 cells present in virus controllers (undetectable viremia in the absence of antiretroviral therapy). We review the mechanisms and clinical consequences for V delta 2 cell depletion in HIV disease. We address the question of whether HIV-mediated V delta 2 cell depletion, despite being an indirect effect of infection, is an important part of the immune evasion strategy for this virus. The important roles for V delta 2 cells, as effectors and immune regulators, identify key mechanisms affected by HIV and show the strong relationships between V delta 2 cell loss and immunodeficiency disease. This field is moving toward immune therapies based on targeting V delta 2 cells and we now have clear goals and expectations to guide interventional clinical trials. Cellular & Molecular Immunology (2013) 10, 42-49; doi:10.1038/cmi.2012.50; Published online: 17 December 2012