Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection
| Autor: | Alasdair Leslie, Nicholas Herbert, Henrik N. Kløverpris, Alveera Singh, Fusi G. Madela, Thumbi Ndung'u, Vukani T. Manzini, Katya Govender, Ntombifuthi Mthabela, Kavidha Reddy, Frank Anderson, Farina Karim, John H. Adamson, Yenzekile Zungu, Faith Nene, Rabiah Fardoos, J Zachary Porterfield, Abigail Ngoepe, Dirhona Ramjit, Osaretin E. Asowata |
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| Rok vydání: | 2020 |
| Předmět: |
CD4-Positive T-Lymphocytes
Younger age T cell Human immunodeficiency virus (HIV) T cells Viremia HIV Infections medicine.disease_cause Lymphocyte Activation Pathogenesis AIDS/HIV 03 medical and health sciences 0302 clinical medicine medicine Humans Large intestine 030212 general & internal medicine 030304 developmental biology 0303 health sciences business.industry Gastroenterology virus diseases General Medicine medicine.disease Small intestine 3. Good health medicine.anatomical_structure Immunology Chronic Disease Duodenum business Research Article |
| Zdroj: | JCI Insight Asowata, O E, Singh, A, Ngoepe, A, Herbert, N, Fardoos, R, Reddy, K, Zungu, Y, Nene, F, Mthabela, N, Ramjit, D, Karim, F, Govender, K, Ndung’u, T, Zachary Porterfield, J, Adamson, J H, Madela, F G, Manzini, V T, Anderson, F, Leslie, A & Kløverpris, H N 2021, ' Irreversible depletion of intestinal CD4 + T cells is associated with T cell activation during chronic HIV infection ', JCI insight, vol. 6, no. 22, e146162 . https://doi.org/10.1172/jci.insight.146162 JCI Insight. |
| ISSN: | 2379-3708 |
| Popis: | HIV infection in the human gastrointestinal (GI) tract is thought to be central to HIV progression, but knowledge of this interaction is primarily limited to cohorts within Westernized countries. Here, we present a large cohort recruited from high HIV endemic areas in South Africa and found that people living with HIV (PLWH) presented at a younger age for investigation in the GI clinic. We identified severe CD4+ T cell depletion in the GI tract, which was greater in the small intestine than in the large intestine and not correlated with years on antiretroviral treatment (ART) or plasma viremia. HIV-p24 staining showed persistent viral expression, particularly in the colon, despite full suppression of plasma viremia. Quantification of mucosal antiretroviral (ARV) drugs revealed no differences in drug penetration between the duodenum and colon. Plasma markers of gut barrier breakdown and immune activation were elevated irrespective of HIV, but peripheral T cell activation was inversely correlated with loss of gut CD4+ T cells in PLWH alone. T cell activation is a strong predictor of HIV progression and independent of plasma viral load, implying that the irreversible loss of GI CD4+ T cells is a key event in the HIV pathogenesis of PLWH in South Africa, yet the underlying mechanisms remain unknown. |
| Databáze: | OpenAIRE |
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