Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection.

Autor:	Asowata OE; Africa Health Research Institute (AHRI), Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa., Singh A; Africa Health Research Institute (AHRI), Durban, South Africa., Ngoepe A; Africa Health Research Institute (AHRI), Durban, South Africa., Herbert N; Africa Health Research Institute (AHRI), Durban, South Africa., Fardoos R; Africa Health Research Institute (AHRI), Durban, South Africa.; Department of Immunology and Microbiology, University of Copenhagen, Denmark., Reddy K; Africa Health Research Institute (AHRI), Durban, South Africa., Zungu Y; Africa Health Research Institute (AHRI), Durban, South Africa., Nene F; Africa Health Research Institute (AHRI), Durban, South Africa., Mthabela N; Africa Health Research Institute (AHRI), Durban, South Africa., Ramjit D; Africa Health Research Institute (AHRI), Durban, South Africa., Karim F; Africa Health Research Institute (AHRI), Durban, South Africa., Govender K; Africa Health Research Institute (AHRI), Durban, South Africa., Ndung'u T; Africa Health Research Institute (AHRI), Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; University College London, Division of Infection and Immunity, London, United Kingdom.; Max Planck Institute for Infection Biology, Berlin, Germany., Porterfield JZ; Africa Health Research Institute (AHRI), Durban, South Africa.; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA., Adamson JH; Africa Health Research Institute (AHRI), Durban, South Africa., Madela FG; Division Upper Gastrointestinal Tract and Colorectal Surgery, Inkosi Albert Luthuli Central Hospital (IALCH), University of KwaZulu-Natal, Durban, South Africa., Manzini VT; Division Upper Gastrointestinal Tract and Colorectal Surgery, Inkosi Albert Luthuli Central Hospital (IALCH), University of KwaZulu-Natal, Durban, South Africa., Anderson F; Division Upper Gastrointestinal Tract and Colorectal Surgery, Inkosi Albert Luthuli Central Hospital (IALCH), University of KwaZulu-Natal, Durban, South Africa., Leslie A; Africa Health Research Institute (AHRI), Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; University College London, Division of Infection and Immunity, London, United Kingdom., Kløverpris HN; Africa Health Research Institute (AHRI), Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; Department of Immunology and Microbiology, University of Copenhagen, Denmark.; University College London, Division of Infection and Immunity, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2021 Nov 22; Vol. 6 (22). Date of Electronic Publication: 2021 Nov 22.
DOI:	10.1172/jci.insight.146162
Abstrakt:	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:	MEDLINE
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