Differential susceptibility of naive, central memory and effector memory T cells to dendritic cell-mediated HIV-1 transmission

Background: Dendritic cells ( DC) have been proposed to facilitate sexual transmission of HIV-1 by capture of the virus in the mucosa and subsequent transmission to CD4(+) T cells. Several T cell subsets can be identified in humans: naive T cells (T-N) that initiate an immune response to new antigens, and memory T cells that respond to previously encountered pathogens. The memory T cell pool comprises central memory (T-CM) and effector memory cells (T-EM), which are characterized by distinct homing and effector functions. The T-EM cell subset, which can be further divided into effector Th1 and Th2 cells, has been shown to be the prime target for viral replication after HIV-1 infection, and is abundantly present in mucosal tissues. Results: We determined the susceptibility of T-N, T-CM and T-EM cells to DC-mediated HIV-1 transmission and found that co-receptor expression on the respective T cell subsets is a decisive factor for transmission. Accordingly, CCR5-using (R5) HIV-1 was most efficiently transmitted to T-EM cells, and CXCR4-using (X4) HIV-1 was preferentially transmitted to T-N cells. Conclusion: The highly efficient R5 transfer to T-EM cells suggests that mucosal T cells are an important target for DC-mediated transmission. This may contribute to the initial burst of virus replication that is observed in these cells. T-N cells, which are the prime target for DC-mediated X4 virus transmission in our study, are considered to inefficiently support HIV-1 replication. Our results thus indicate that DC may play a decisive role in the susceptibility of T-N cells to X4 tropic HIV-1.