Differential susceptibility of resting CD4+ T lymphocytes to a T-tropic and a macrophage (M)-tropic human immunodeficiency virus type 1 is associated with their surface expression of CD38 molecules

Recent evidence has accumulated which definitively shows that chemokine receptors CCR5 and CXCR4 play an essential role as coreceptors for human immunodeficiency virus type 1 (HIV-1) infection. Flow cytometric analysis permitted us to detect CD38, a surface marker of early differentiation, as well as activation of T cells, on about half of healthy donor-derived CD4+ T cells. In this study, we focused on the susceptibility of CD38+ and CD38− subsets of CD4+ T cells to HIV-1 infection with different coreceptor tropisms. About 20% of peripheral blood mononuclear cell-derived resting CD4+ T cells were recovered into the CD38+ subset fraction by panning with a monoclonal antibody to CD38. Most of the cells in this CD38high fraction also expressed CD45RA and CD62L at higher intensities compared with those of CD38low fraction. CCR5+ T cells predominated in the CD38− subset, although cell surface expression of CD4 and CXCR4 was almost similar between both subsets. This difference was consistent with a significantly higher susceptibility of the CD38− subset to a macrophage (M)-tropic HIV-1 strain. In contrast, it was shown that a T-tropic strain of HIV-1 could replicate more efficiently in the CD38+ subset, although viral adsorption rates were similar between both subsets. Thus, the differential susceptibility of CD4+ T cells to M− and T-tropic HIV-1 was associated with their surface expression of CD38.