Early antiretroviral therapy-treated perinatally HIV-infected seronegative children demonstrate distinct long-term persistence of HIV-specific T-cell and B-cell memory
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
|---|---|
| Enthalten in: |
AIDS (London, England) - 34(2020), 5 vom: 01. Apr., Seite 669-680 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cotugno, Nicola [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anti-Retroviral Agents |
|---|
| Anmerkungen: |
Date Completed 18.02.2021 Date Revised 05.10.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1097/QAD.0000000000002485 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM307560848 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM307560848 | ||
| 003 | DE-627 | ||
| 005 | 20231225125831.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1097/QAD.0000000000002485 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1025.xml |
| 035 | |a (DE-627)NLM307560848 | ||
| 035 | |a (NLM)32167989 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cotugno, Nicola |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Early antiretroviral therapy-treated perinatally HIV-infected seronegative children demonstrate distinct long-term persistence of HIV-specific T-cell and B-cell memory |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.02.2021 | ||
| 500 | |a Date Revised 05.10.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-Retroviral Agents |2 NLM | |
| 700 | 1 | |a Morrocchi, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Rinaldi, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Rocca, Salvatore |e verfasserin |4 aut | |
| 700 | 1 | |a Pepponi, Ilaria |e verfasserin |4 aut | |
| 700 | 1 | |a di Cesare, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Bernardi, Stefania |e verfasserin |4 aut | |
| 700 | 1 | |a Zangari, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Pallikkuth, Suresh |e verfasserin |4 aut | |
| 700 | 1 | |a de Armas, Lesley |e verfasserin |4 aut | |
| 700 | 1 | |a Levy, Ofer |e verfasserin |4 aut | |
| 700 | 1 | |a Rossi, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Pahwa, Savita |e verfasserin |4 aut | |
| 700 | 1 | |a Palma, Paolo |e verfasserin |4 aut | |
| 700 | 0 | |a EPIICAL Consortium |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t AIDS (London, England) |d 1988 |g 34(2020), 5 vom: 01. Apr., Seite 669-680 |w (DE-627)NLM012619280 |x 1473-5571 |7 nnns |
| 773 | 1 | 8 | |g volume:34 |g year:2020 |g number:5 |g day:01 |g month:04 |g pages:669-680 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1097/QAD.0000000000002485 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 34 |j 2020 |e 5 |b 01 |c 04 |h 669-680 | ||