Early antiretroviral therapy-treated perinatally HIV-infected seronegative children demonstrate distinct long-term persistence of HIV-specific T-cell and B-cell memory. (1st April 2020)

• Record Type: Journal Article
• Authors: Cotugno, Nicola; Morrocchi, Elena; Rinaldi, Stefano; Rocca, Salvatore; Pepponi, Ilaria; di Cesare, Silvia; Bernardi, Stefania; Zangari, Paola; Pallikkuth, Suresh; de Armas, Lesley; Levy, Ofer; Rossi, Paolo; Pahwa, Savita; Palma, Paolo
• Is Part Of: AIDS. Volume 34:Number 5(2020)
• Publication Date: 2020-04-01
• Subjects: early treated children -- gene expression -- HIV-specific B cells -- HIV-specific cell immunity -- HIV-specific T cells -- pediatric HIV -- seronegative early treated children; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000002485
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life. Design: Twenty perinatally HIV-infected children who received ART therapy within the first year of life (early treated) and with stable viral control (>5 years) were grouped according to their serological response to HIV. Methods: Western blot analysis and ELISA defined 14 HIV-seropositive and six seronegative patients. Frequencies of gp140-specific T-cell and B-cell, and T-cell cytokine production were quantified by flow cytometry in both seronegatives and seropositives. Transcriptional signatures in purified gp140-specific B-cell subsets, in response to in-vitro stimulation with HIV peptides was evaluated by multiplex RT-PCR. Results: Gp140-specific T cells and B cells persist at similar levels in both groups. A higher production of IL-21 in gp140-specific T cells was found in seropositives vs. seronegatives ( P = 0.003). Gene expression in switched IgM−IgD− gp140-specific memory B cells after stimulation with HIV peptides in vitro demonstrated a differential expression of genes involved in signal transduction and activation after BCR/TLR triggering and B-cell activation. Genes relating to antibody production (PRDM1) and T–B cognate stimulation (CXCR4, IL21R) were differentially induced after in-vitro stimulation in seronegatives vs. seropositives suggesting a truncated process of B-cell maturation. Conclusion: HIV-specific memory B and T cells persist in early treated regardless their serological status. Seronegatives and seropositives are distinguished by gp140-specific T-cell function and by distinct transcriptional signatures of gp140-specific B cells after in-vitro stimulation, presumably because of a different antigen exposure. Such qualitative insights may inform future immunotherapeutic interventions. Abstract : Supplemental Digital Content is available in the text