Gag-Specific CD8 T-Cell Proliferation Is Associated With Higher Peripheral Blood Levels of Transforming Growth Factor-β and Gut-Homing T Cells in Youths Perinatally Infected With Human Immunodeficiency Virus-1: The ANRS-EP38-IMMIP Study

International audienceBackground: Gag-specific T lymphocytes play a key role in the control of HIV replication. Their restoration will be important for future reservoir targeting strategies. Here, we aimed to identify immune correlates of Gag-specific CD8 T-cell proliferation in youths with perinatally acquired HIV-1 infection. Methods: The ANRS-EP38-IMMIP study included youths of 15 to 24 years of age. Fifty-three were taking cART and aviremic at the time of the study and had undergone valid CFSE-based flow cytometry T-cell proliferation assays. Plasma analytes were quantified by ELISA or multiplex assays. Peripheral blood cells were phenotyped by flow cytometry. Logistic regression was used to study the association between Gag-specific T-cell proliferation and immune markers. Results: Patients with Gag-specific CD8 T-cell proliferation had higher levels of plasma TGF-β1, a lower proportion of naive cells among Tregs, and higher percentages of CD4 and CD8 T cells expressing the α4β7 integrin or CD161 molecule than those without a Gag-specific response. These associations were significant based on analyses including potential confounders. Conclusion: Preserved Gag-specific CD8 T-cell proliferation was associated with higher TGF-β1 levels and increased percentages of T cells with a gut-homing phenotype at least 15 years after HIV infection during the perinatal period