Journal
AIDS
Volume 34, Issue 5, Pages 669-680Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000002485
Keywords
early treated children; gene expression; HIV-specific B cells; HIV-specific cell immunity; HIV-specific T cells; pediatric HIV; seronegative early treated children
Categories
Funding
- PENTA-ID foundation
- independent ViiV Healthcare UK grant
- CFAR [P30AI073961]
- NIAID
- NCI
- NICHD
- NHLBI
- NIDA
- NIMH
- NIA
- NIDDK
- NIGMS
- FIC
- OAR
- Children's Hospital Bambino Gesu
- Associazione Volontari Bambino Gesu
- National Institute of Health/National Institute of Allergy and Infectious Diseases Division of AIDS [U19AI118608]
- Department of Pediatrics, Boston Children's Hospital
- [AI12734704]
- [AI108472]
- [AI127347]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available