Login / Signup

HIV-1 DNA and Immune Activation Levels Differ for Long-Lived T-Cells in Lymph Nodes, Compared with Peripheral Blood, during Antiretroviral Therapy.

Christina Mallarino-HaegerMaria PinoElise G VioxAmélie PagliuzzaColin T KingKevin NguyenJustin L HarperSol Del Mar AldreteBarbara CervasiKeith A DelmanMichael C LoweNicolas ChomontVincent C MarconiMirko Paiardini
Published in: Journal of virology (2023)
Elucidating the mechanisms underlying the persistence and location of the HIV reservoir is critical for developing cure interventions. While it has been shown that levels of T-cell activation and the size of the HIV reservoir are greater in rectal tissue and lymph nodes (LN) than in blood, the relative contributions of T-cell subsets to this anatomic difference are unknown. We measured and compared HIV-1 DNA content, expression of the T-cell activation markers CD38 and HLA-DR, and expression of the exhaustion markers programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) in naive, central memory (CM), transitional memory (TM), and effector memory (EM) CD4 + and CD8 + T-cells in paired blood and LN samples among 14 people with HIV who were receiving antiretroviral therapy. HIV-1 DNA levels, T-cell immune activation, and TIGIT expression were higher in LN than in blood, especially in CM and TM CD4 + T-cell subsets. Immune activation was significantly higher in all CD8 + T-cell subsets, and memory CD8 + T-cell subsets from LN had higher levels of PD-1 expression, compared with blood, while TIGIT expression levels were significantly lower in TM CD8 + T-cells. The differences seen in CM and TM CD4 + T-cell subsets were more pronounced among participants with CD4 + T-cell counts of <500 cells/μL within 2 years after antiretroviral therapy initiation, thus highlighting increased residual dysregulation in LN as a distinguishing feature of and a potential mechanism for individuals with suboptimal CD4 + T-cell recovery during antiretroviral therapy. IMPORTANCE This study provides new insights into the contributions of different CD4 + and CD8 + T-cell subsets to the anatomic differences between LN and blood in individuals with HIV who have optimal versus suboptimal CD4 + T-cell recovery. To our knowledge, this is the first study comparing paired LN and blood CD4 + and CD8 + T-cell differentiation subsets, as well as those subsets in immunological responders versus immunological suboptimal responders.
Keyphrases