Phenotypic Analysis of Peripheral Blood γδ T Lymphocytes and Their Targeting by Human Immunodeficiency Virus Type 1 in Vivo

There is increasing evidence that a wider range of lymphoid cell types other than CD4+ T helper lymphocytes are infected with HIV-1 in vivo, including CD8 lymphocytes, natural killer cells, and reticulodendritic cells. Each potentially contributes to the reservoir of infected cells that resist antiviral treatment and to the impairment of immune responses in AIDS. By quantitative PCR for HIV proviral sequences we have now obtained evidence for substantial infection of γδ lymphocytes, contributing 3–45% of the proviral load in peripheral blood. A large proportion of γδ lymphocytes constitutively expressed the chemokine receptors CCR5 and CXCR4, with evidence for marked up-regulation of CD8 in samples from HIV-infected individuals, corresponding to an activated phenotype. That γδ lymphocytes might be susceptible to HIV infection was investigated using in vitro infectivity assays of recombinant HIV-expressing green fluorescent protein, followed by flow cytometry. γδ, CD4, and CD8 lymphocytes were each productively infected, with γδ lymphocytes showing the greatest susceptibility. For each cell type, blocking assays with an anti-CD4 monoclonal antibody indicated that entry was CD4-dependent.