Project

HIV infects and depletes CD4+ T cells, leading to a progressive loss of adaptive immune responses and ultimately to AIDS. In addition, HIV preferentially targets HIV-specific CD4+ T cells, resulting in an attrition of the very cells that should orchestrate the antiviral immune response. Due to this preferential depletion, HIV-specific CD4+ T cells are few and remain incompletely characterized. The emergence of single cell technologies opens the opportunity for an in depth analysis of the rare specific CD4+ T cells that persist in the circulation of chronically infected patients. We have sorted single CD4+ T cells specific for the most immunodominant epitope in HIV-1 capsid, using an optimized MHC class II tetramer labeling protocol. We now propose to analyze these single cells by multiplexed real time PCR in a microfluidics device, to define their transcriptional profile. We will analyze the differentiation status of HIV-specific CD4+ T cells in rare patients who naturally control HIV infection and in progressor patients who control HIV replication due to antiretroviral therapy. This project will help define the parameters of an efficient T cell response against HIV, and may provide insights into the type of responses that should be induced by candidate HIV vaccines.