Intestinal Tissue-Resident Memory T Cells and HIV-1 Persistence During Antiretroviral Therapy (ANRSGALT-2)
Intestinal Tissue-Resident Memory T Cells in HIV-1 Infection: Mechanisms Involved in Their Depletion and Role in Viral Persistence During Antiretroviral Therapy
調査の概要
詳細な説明
Tissue-resident memory T lymphocytes (TRM) are a specialized population of memory T cells that reside permanently within tissues and play a central role in local immune defense. In HIV-1 infection, the intestinal mucosa represents a major site of viral replication, immune dysfunction, and long-term viral persistence despite effective antiretroviral therapy (ART). Intestinal CD4+ T cells are highly susceptible to HIV-1 infection and undergo profound depletion early during infection, while incomplete immune restoration persists under ART.
Emerging evidence suggests that intestinal TRM CD4+ cells may be particularly susceptible to HIV-1 infection and may contribute to the maintenance of viral reservoirs because of their long lifespan and tissue retention properties. In parallel, TRM CD8+ cells may participate in local antiviral immune responses, although their functions may be impaired in the chronic inflammatory environment associated with HIV infection.
The objectives of this physiopathological study are to improve understanding of the mechanisms involved in defective restoration of intestinal TRM populations during suppressive ART and to evaluate the contribution of TRM CD4+ cells to HIV-1 persistence. Exploratory objectives include the phenotypic, transcriptomic, and functional characterization of intestinal TRM CD4+ and CD8+ cells; assessment of the susceptibility of intestinal TRM CD4+ cells to HIV-1 infection; evaluation of their role as viral reservoirs, including intact proviruses; and investigation of mechanisms regulating tissue retention and recirculation of ex-TRM cells in the intestinal mucosa.
This is a monocentric interventional physiopathological study with minimal risks and constraints (RIPH2). The study will enroll 20 people living with HIV-1 receiving suppressive ART and 10 HIV-seronegative controls matched for age and sex. Participants will be recruited among individuals undergoing routine colonoscopy, particularly for colorectal cancer screening indications. Study procedures consist of additional colonic mucosal biopsies collected during the clinically indicated colonoscopy and blood sampling performed on the day of the procedure.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Pierre Delobel, MD, PhD
- 電話番号：+33 5 61 77 75 08
- メール：delobel.p@chu-toulouse.fr
研究連絡先のバックアップ
- 名前：Marcia Trumeau, MS
- メール：marcia.trumeau@anrs.fr
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
I - Inclusion criteria
1 - Group 1: People Living With HIV-1
- Age ≥ 18 years
- Documented HIV-1 infection
- Continuous suppressive antiretroviral therapy initiated during chronic infection for at least 12 months
- Plasma HIV-1 RNA ≤ 50 copies/mL for at least 6 months under ART (one isolated blip ≤ 200 copies/mL allowed)
- Blood CD4+ T-cell count ≥ 350 cells/mm³
- Clinically indicated colonoscopy independent of the research protocol
- Affiliation with a social security system
Written informed consent obtained before any study-specific procedure
2- Group 2: HIV-Seronegative Controls
- Age ≥ 18 years
- HIV-seronegative status
- Clinically indicated colonoscopy independent of the research protocol
- Affiliation with a social security system
- Written informed consent obtained before any study-specific procedure
II - Exclusion Criteria
Group 1: People Living With HIV-1
- HIV-2 infection
- Inflammatory bowel disease (Crohn's disease or ulcerative colitis) or celiac disease
- Platelet count < 50 G/L or uncorrectable coagulation disorders contraindicating biopsies
- Decompensated cirrhosis
- History of lymphoma
- Participation in an HIV vaccine or immunotherapy study
- Pregnant or breastfeeding women
- Participation in another clinical study with an ongoing exclusion period
- Vulnerable individuals, including minors, individuals under guardianship, or persons deprived of liberty
Group 2: HIV-Seronegative Controls
- HIV-1 or HIV-2 infection
- Refusal to undergo HIV serology testing
- Inflammatory bowel disease (Crohn's disease or ulcerative colitis) or celiac disease
- Platelet count < 50 G/L or uncorrectable coagulation disorders contraindicating biopsies
- Decompensated cirrhosis
- History of lymphoma
- Pregnant or breastfeeding women
- Participation in another clinical study with an ongoing exclusion period
- Vulnerable individuals, including minors, individuals under guardianship, or persons deprived of liberty
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：HIV-1-Infected Participants Receiving Suppressive Antiretroviral Therapy
Participants living with HIV-1 receiving suppressive antiretroviral therapy (ART) and undergoing clinically indicated colonoscopy will undergo blood sampling and additional colonic mucosal biopsies for immunological and virological analyses.
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Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
他の名前：
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実験的：HIV-Seronegative Controls
HIV-seronegative participants undergoing clinically indicated colonoscopy will undergo blood sampling and additional colonic mucosal biopsies for immunological analyses.
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Collection of blood samples and additional colonic mucosal biopsies during clinically indicated colonoscopy for immunological and virological analyses.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Frequency and Immunophenotypic Profile of Intestinal CD4+ and CD8+ Tissue-Resident Memory T Cells Measured by Multiparameter Flow Cytometry
時間枠：Day 1
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Frequency and expression of tissue-resident memory T-cell markers (CD69, CD103, CCR7, S1PR1), differentiation markers (CD45RA/RO, CD27, CD28), survival markers (CD127, TCF-1), activation and exhaustion markers (HLA-DR, CD38, CD57, KLRG1, CD101, PD-1, TIGIT, TIM-3, CD39), and homing markers (CD49d, β7, CCR5, CCR6, CXCR3, CXCR6, CX3CR1) on intestinal CD4+ and CD8+ T cells measured by multiparameter flow cytometry on colonic mucosal biopsy specimens.
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Day 1
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Single-Cell Transcriptomic and T-Cell Receptor Repertoire Profiles of Intestinal Tissue-Resident Memory T Cells Measured by CITE-seq
時間枠：Day 1
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Single-cell transcriptomic profiles and T-cell receptor repertoire of intestinal CD4+ and CD8+ tissue-resident memory T cells measured using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq).
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Day 1
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Total and Intact HIV-1 Proviral DNA Levels in Intestinal CD4+ Tissue-Resident Memory T Cells Measured by Multiplex ddPCR Intact Proviral DNA Assay (IPDA)
時間枠：Day 1
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Quantification of total and intact HIV-1 proviral DNA in intestinal CD4+ tissue-resident memory T cells isolated from colonic mucosal biopsy specimens using multiplex droplet digital PCR Intact Proviral DNA Assay (IPDA).
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Day 1
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Cytokine Production, Degranulation, and Proliferative Capacity of Intestinal Tissue-Resident Memory T Cells Measured by Functional Flow Cytometry Assays
時間枠：Day 1
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Production of IL-2, IFN-γ, TNF-α, IL-10, IL-17, granzyme, and perforin, together with proliferative capacity following antigenic stimulation, measured in intestinal tissue-resident memory T cells using functional flow cytometry assays.
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Day 1
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協力者と研究者
捜査官
- 主任研究者：Pierre Delobel, MD, PhD、University Hospital of Toulouse
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- ANRS 00853-R-PR GALT-2
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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