Abstract
The persistence of the human immunodeficiency virus (HIV) in infected individuals undergoing treatment is a major characteristic of the infection and the main obstacle to achieving a cure. Therefore, a better understanding of the lymphocyte populations forming the cellular reservoir of HIV is still highly needed. The participation of conventional T cells with TCRαβ is already well described in the literature. This thesis aims to explore non-conventional invariant or semi-invariant TCR cells as potential HIV targets. To this end we: i) analyzed their concentration in blood according to the clinical profiles of people living with HIV (PLHIV), ii) assessed the proportion of unconventional lymphocytes expressing CD4, CCR5, and CXCR4 receptors, as well as the density of these HIV entry receptors, iii) validated the digital PCR (dPCR) approach and we have showed that dPCR is more accurate than real-time qPCR (qPCR) for HIV DNA quantification.The expression of the CD4 receptor and the HIV co-receptors, CCR5 and CXCR4, was studied in TCRVα7.2 cells described according to their co-expression of the CD161 marker into CD161-, CD161+ or MAIT-like and CD161bright or MAIT cells, NKT cells and TCRγδ cells divided into three subpopulations: Vδ1, Vδ2, and Vδ* (representing neither δ1 nor δ2 cells, describing the Vδ3 and Vδ5 cells). This comparative study demonstrated preferential depletion of the Vδ2 LTγδ populations and CD4 MAIT cells, while other subpopulations were found to be more frequent under effective treatment: no-Vδ1 and no-Vδ2 LTγδ and TCRVα7.2+ CD161-. These TCRVα7.2+ CD161- cells and Vδ* LTγδ are two populations with a high potential of participation in the HIV reservoir due to their expression of CD4 and the co-receptors CCR5 and CXCR4.The relative quantification of the HIV reservoir in these cells requires a more accurate technique than qPCR. A dPCR technique was developed and compared analytically to the qPCR technique used routinely in the laboratory. Because of its low sample volume requirement and better reproducibility, dPCR will allow us to more accurately quantify HIV DNA in TCRVα7.2+ CD161- and LTγδ Vδ* cells to determine their participation in the HIV reservoir.