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Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals
Maud Mavigner, … , Jacques Izopet, Pierre Delobel
Maud Mavigner, … , Jacques Izopet, Pierre Delobel
Published December 12, 2011
Citation Information: J Clin Invest. 2012;122(1):62-69. https://doi.org/10.1172/JCI59011.
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Research Article AIDS/HIV

Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals

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Abstract

Depletion of CD4+ T cells from the gut occurs rapidly during acute HIV-1 infection. This has been linked to systemic inflammation and disease progression as a result of translocation of microbial products from the gut lumen into the bloodstream. Combined antiretroviral therapy (cART) substantially restores CD4+ T cell numbers in peripheral blood, but the gut compartment remains largely depleted of such cells for poorly understood reasons. Here, we show that a lack of recruitment of CD4+ T cells to the gut could be involved in the incomplete mucosal immune reconstitution of cART-treated HIV-infected individuals. We investigated the trafficking of CD4+ T cells expressing the gut-homing receptors CCR9 and integrin α4β7 and found that many of these T cells remained in the circulation rather than repopulating the mucosa of the small intestine. This is likely because expression of the CCR9 ligand CCL25 was lower in the small intestine of HIV-infected individuals. The defective gut homing of CCR9+β7+ CD4+ T cells — a population that we found included most gut-homing Th17 cells, which have a critical role in mucosal immune defense — correlated with high plasma concentrations of markers of mucosal damage, microbial translocation, and systemic T cell activation. Our results thus describe alterations in CD4+ T cell homing to the gut that could prevent efficient mucosal immune reconstitution in HIV-infected individuals despite effective cART.

Authors

Maud Mavigner, Michelle Cazabat, Martine Dubois, Fatima-Ezzahra L’Faqihi, Mary Requena, Christophe Pasquier, Pascale Klopp, Jacques Amar, Laurent Alric, Karl Barange, Jean-Pierre Vinel, Bruno Marchou, Patrice Massip, Jacques Izopet, Pierre Delobel

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Figure 1

CD4+ T cell depletion and HIV-1 persistence in the gut mucosa of HIV-infected individuals despite sustained effective cART.

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CD4+ T cell depletion and HIV-1 persistence in the gut mucosa of HIV-inf...
(A) Frequencies of CD4+ in CD3+ T cells in the peripheral blood (PB) and jejunum mucosa of HIV-infected individuals (n = 20) and uninfected individuals (n = 9). Percentages of cells were determined by flow cytometry. Horizontal lines indicate median values. Each symbol represents an individual. (B) Absolute numbers of CD4+ T cells per surface unit of jejunum mucosa in HIV-infected individuals (n = 20) and uninfected individuals (n = 9). Horizontal lines indicate median values. Each symbol represents an individual. Immunohistochemical detection of intestinal CD4+ T cells (brown staining) in a representative HIV-infected individual and an uninfected control are shown. Original magnification, ×100. (C) Correlation between the frequency of CD4+ in CD3+ T cells in peripheral blood and jejunum mucosa (n = 20 HIV-infected individuals, and n = 9 uninfected individuals). Percentages of cells were determined by flow cytometry. Each symbol represents an individual. (D) Paired HIV-1 DNA loads in CD4+ T cells of the peripheral blood and jejunum mucosa (n = 20). HIV-1 DNA was quantified by real-time PCR.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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