Identification of a CCR5-expressing T cell subset that is resistant to R5-tropic HIV infection

Abstract

Infection with HIV-1 perturbs homeostasis of human T cell subsets, leading to accelerated immunologic deterioration. While studying changes in CD4 + memory and naíve T cells during HIV-1 infection, we found that a subset of CD4+ effector memory T cells that are CCR7 -CD45RO-CD45RA+ (referred to as T EMRA cells), was significantly increased in some HIV-infected individuals. This T cell subset displayed a differentiated phenotype and skewed Th1-type cytokine production. Despite expressing high levels of CCR5, T EMRA cells were strikingly resistant to infection with CCR5 (R5)-tropic HIV-1, but remained highly susceptible to CXCR4 (X4)-tropic HIV-1. The resistance of TEMRA cells to R5-tropic viruses was determined to be post-entry of the virus and prior to early viral reverse transcription, suggesting a block at the uncoating stage. Remarkably, in a subset of the HIV-infected individuals, the relatively high proportion of TEMRA cells within effector T cells strongly correlated with higher CD4+ T cell numbers. These data provide compelling evidence for selection of an HIV-1-resistant CD4+ T cell population during the course of HIV-1 infection. Determining the host factors within TEMRA cells that restrict R5-tropic viruses and endow HIV-1-specific CD4+ T cells with this ability may result in novel therapeutic strategies against HIV-1 infection. © 2007 Oswald-Richter et al.