Ferroptosis and Dysfunction of CD3+CD4−CD8− T Cells are Associated with Poor Immune Reconstitution in HIV Patients

Our study centered on the proliferation, activation, ferroptosis, killing function, and inflammatory status of DNT cells in INRs. We found that DNT cells in INRs had more active proliferation and activation, weakened killing function, mitochondrial function with typical ferroptosis features, and increased TNF-αlevels. Correlation analysis indicated that DNT cell overactivation (Ki-67+, CD38+HLA-DR+), MMP reduction ratio, and TNF-αexpression were negatively related to immune reconstitution in PLHIVs. In contrast, the killing function (perforin+) of DNT cells was positively related to it. These findings provide a theoretical basis for targeting the functional remodeling of DNT cells. In the future, therapeutic strategies can be explored, such as regulating the mitochondrial metabolic pathway or enhancing the immunoregulatory activity of DNT cells. These strategies can thus offer innovative solutions to the dilemma of immune reconstitution in HIV-infected individuals.