scholarly journals Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Gerald Mak ◽  
John J. Zaunders ◽  
Michelle Bailey ◽  
Nabila Seddiki ◽  
Geraint Rogers ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Microbial Translocation ◽  
People Living With Hiv ◽  
Epithelial Permeability ◽  
Primary Hiv Infection ◽  
Mucosal Barrier Function ◽  
Gastrointestinal Barrier

BackgroundDespite successful ART in people living with HIV infection (PLHIV) they experience increased morbidity and mortality compared with HIV-negative controls. A dominant paradigm is that gut-associated lymphatic tissue (GALT) destruction at the time of primary HIV infection leads to loss of gut integrity, pathological microbial translocation across the compromised gastrointestinal barrier and, consequently, systemic inflammation. We aimed to identify and measure specific changes in the gastrointestinal barrier that might allow bacterial translocation, and their persistence despite initiation of antiretroviral therapy (ART).MethodWe conducted a cross-sectional study of the gastrointestinal (GIT) barrier in PLHIV and HIV-uninfected controls (HUC). The GIT barrier was assessed as follows: in vivo mucosal imaging using confocal endomicroscopy (CEM); the immunophenotype of GIT and circulating lymphocytes; the gut microbiome; and plasma inflammation markers Tumour Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6); and the microbial translocation marker sCD14.ResultsA cohort of PLHIV who initiated ART early, during primary HIV infection (PHI), n=5), and late (chronic HIV infection (CHI), n=7) infection were evaluated for the differential effects of the stage of ART initiation on the GIT barrier compared with HUC (n=6). We observed a significant decrease in the CD4 T-cell count of CHI patients in the left colon (p=0.03) and a trend to a decrease in the terminal ileum (p=0.13). We did not find evidence of increased epithelial permeability by CEM. No significant differences were found in microbial translocation or inflammatory markers in plasma. In gut biopsies, CD8 T-cells, including resident intraepithelial CD103+ cells, did not show any significant elevation of activation in PLHIV, compared to HUC. The majority of residual circulating activated CD38+HLA-DR+ CD8 T-cells did not exhibit gut-homing integrins α4ß7, suggesting that they did not originate in GALT. A significant reduction in the evenness of species distribution in the microbiome of CHI subjects (p=0.016) was observed, with significantly higher relative abundance of the genus Spirochaeta in PHI subjects (p=0.042).ConclusionThese data suggest that substantial, non-specific increases in epithelial permeability may not be the most important mechanism of HIV-associated immune activation in well-controlled HIV-positive patients on antiretroviral therapy. Changes in gut microbiota warrant further study.

Antiretroviral therapy initiation during primary HIV infection enhances both CD127 expression and the proliferative capacity of HIV-specific CD8+ T cells

AIDS ◽  
2009 ◽  
Vol 23 (13) ◽  
pp. 1649-1658 ◽  
Author(s):  
Camille Lécuroux ◽  
Isabelle Girault ◽  
François Boutboul ◽  
Alejandra Urrutia ◽  
Cécile Goujard ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Proliferative Capacity ◽  
Primary Hiv Infection ◽  
Therapy Initiation ◽  
Cd127 Expression

Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection

AIDS ◽  
2002 ◽  
Vol 16 (4) ◽  
pp. 589-596 ◽  
Author(s):  
Richard Tilling ◽  
Sabine Kinloch ◽  
Li-Ean Goh ◽  
David Cooper ◽  
Luc Perrin ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Primary Hiv Infection ◽  
Highly Active

scholarly journals CD8+T Cells Specific for EBV, Cytomegalovirus, and Influenza Virus Are Activated during Primary HIV Infection

2004 ◽  
Vol 173 (4) ◽  
pp. 2410-2418 ◽  
Author(s):  
Jean-Marc Doisne ◽  
Alejandra Urrutia ◽  
Christine Lacabaratz-Porret ◽  
Cécile Goujard ◽  
Laurence Meyer ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Primary Hiv Infection

Identification of a particular HIV-specific CD8+ T-cell subset with a CD27+ CD45RO−/RA+ phenotype and memory characteristics after initiation of HAART during acute primary HIV infection

Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3209-3217 ◽  
Author(s):  
Camille Lécuroux ◽  
Isabelle Girault ◽  
Alejandra Urrutia ◽  
Jean-Marc Doisne ◽  
Christiane Deveau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Highly Active Antiretroviral Therapy ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Resting Cells ◽  
Primary Hiv Infection ◽  
Memory Characteristics

AbstractCD8+ T cells play an important role in controlling viral infections. Defective CD8+ T-cell responses during HIV infection could contribute to viral persistence. Early initiation of highly active antiretroviral therapy during acute primary HIV infection helps to preserve HIV-specific immune responses. Here, we describe a particular CD27+ CD45RO−/RA+ HIV-specific CD8+ T cell in participants treated early during the primary infection. These cells, which were present at a very low frequency during primary HIV infection, increased markedly after early treatment, whereas their frequency remained unchanged in untreated participants and in participants treated later. These nonnaive antigen-experienced cells are in a resting state and have characteristics of long-lived memory cells. They also possess direct effector capabilities, such as cytokine production, and are able to proliferate and to acquire cytotoxic functions on reactivation. Our results suggest that these HIV-specific CD27+ CD45RO−/RA+ CD8+ T cells, observed when early viral replication is inhibited, form a pool of resting cells with memory characteristics.

scholarly journals Novel CD4-Based Bispecific Chimeric Antigen Receptor Designed for Enhanced Anti-HIV Potency and Absence of HIV Entry Receptor Activity

2015 ◽  
Vol 89 (13) ◽  
pp. 6685-6694 ◽  
Author(s):  
Li Liu ◽  
Bhavik Patel ◽  
Mustafa H. Ghanem ◽  
Virgilio Bundoc ◽  
Zhili Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Chimeric Antigen Receptor ◽  
Cd8 T Cells ◽  
Genetically Engineered ◽  
Functional Cure ◽  
Gp120 Subunit ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTAdoptive transfer of CD8 T cells genetically engineered to express “chimeric antigen receptors” (CARs) represents a potential approach toward an HIV infection “functional cure” whereby durable virologic suppression is sustained after discontinuation of antiretroviral therapy. We describe a novel bispecific CAR in which a CD4 segment is linked to a single-chain variable fragment of the 17b human monoclonal antibody recognizing a highly conserved CD4-induced epitope on gp120 involved in coreceptor binding. We compared a standard CD4 CAR with CD4-17b CARs where the polypeptide linker between the CD4 and 17b moieties is sufficiently long (CD4-35-17b CAR) versus too short (CD4-10-17b) to permit simultaneous binding of the two moieties to a single gp120 subunit. When transduced into a peripheral blood mononuclear cell (PBMC) or T cells thereof, all three CD4-based CARs displayed specific functional activities against HIV-1 Env-expressing target cells, including stimulation of gamma interferon (IFN-γ) release, specific target cell killing, and suppression of HIV-1 pseudovirus production. In assays of spreading infection of PBMCs with genetically diverse HIV-1 primary isolates, the CD4-10-17b CAR displayed enhanced potency compared to the CD4 CAR whereas the CD4-35-17b CAR displayed diminished potency. Importantly, both CD4-17b CARs were devoid of a major undesired activity observed with the CD4 CAR, namely, rendering the transduced CD8+T cells susceptible to HIV-1 infection. Likely mechanisms for the superior potency of the CD4-10-17b CAR over the CD4-35-17b CAR include the greater potential of the former to engage in the serial antigen binding required for efficient T cell activation and the ability of two CD4-10-17b molecules to simultaneously bind a single gp120 subunit.IMPORTANCEHIV research has been energized by prospects for a cure for HIV infection or, at least, for a “functional cure” whereby antiretroviral therapy can be discontinued without virus rebound. This report describes a novel CD4-based “chimeric antigen receptor” (CAR) which, when genetically engineered into T cells, gives them the capability to selectively respond to and kill HIV-infected cells. This CAR displays enhanced features compared to previously described CD4-based CARs, namely, increased potency and avoidance of the undesired rendering of the genetically modified CD8 T cells susceptible to HIV infection. When adoptively transferred back to the individual, the genetically modified T cells will hopefully provide durable killing of infected cells and sustained virus suppression without continued antiretroviral therapy, i.e., a functional cure.

scholarly journals Higher CD27+CD8+ T Cells Percentages during Suppressive Antiretroviral Therapy Predict Greater Subsequent CD4+ T Cell Recovery in Treated HIV Infection

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84091 ◽  
Author(s):  
Lillian Seu ◽  
Gabriel M. Ortiz ◽  
Lorrie Epling ◽  
Elizabeth Sinclair ◽  
Louise A. Swainson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Cell Recovery

scholarly journals Peculiar Phenotypic and Cytotoxic Features of Pulmonary Mucosal CD8 T Cells in People Living with HIV Receiving Long-Term Antiretroviral Therapy

2020 ◽  
pp. ji2000916
Author(s):  
Oussama Meziane ◽  
Yulia Alexandrova ◽  
Ronald Olivenstein ◽  
Franck P. Dupuy ◽  
Syim Salahuddin ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
People Living With Hiv ◽  
Living With Hiv

scholarly journals Residual Viremia Is Linked to a Specific Immune Activation Profile in HIV-1-Infected Adults Under Efficient Antiretroviral Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Mehwish Younas ◽  
Christina Psomas ◽  
Christelle Reynes ◽  
Renaud Cezar ◽  
Lucy Kundura ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Concentration ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
Immune Activation ◽  
Microbial Translocation ◽  
The Other ◽  
Low Level ◽  
Activation Profile ◽  
Hiv 1

Chronic immune activation persists in persons living with HIV-1 even though they are aviremic under antiretroviral therapy, and fuels comorbidities. In previous studies, we have revealed that virologic responders present distinct profiles of immune activation, and that one of these profiles is related to microbial translocation. In the present work, we tested in 140 HIV-1-infected adults under efficient treatment for a mean duration of eight years whether low-level viremia might be another cause of immune activation. We observed that the frequency of viremia between 1 and 20 HIV-1 RNA copies/mL (39.5 ± 24.7% versus 21.1 ± 22.5%, p = 0.033) and transient viremia above 20 HIV-1 RNA copies/mL (15.1 ± 16.9% versus 3.3 ± 7.2%, p = 0.005) over the 2 last years was higher in patients with one profile of immune activation, Profile E, than in the other patients. Profile E, which is different from the profile related to microbial translocation with frequent CD38+ CD8+ T cells, is characterized by a high level of CD4+ T cell (cell surface expression of CD38), monocyte (plasma concentration of soluble CD14), and endothelium (plasma concentration of soluble Endothelial Protein C Receptor) activation, whereas the other profiles presented low CD4:CD8 ratio, elevated proportions of central memory CD8+ T cells or HLA-DR+ CD4+ T cells, respectively. Our data reinforce the hypothesis that various etiological factors shape the form of the immune activation in virologic responders, resulting in specific profiles. Given the type of immune activation of Profile E, a potential causal link between low-level viremia and atherosclerosis should be investigated.

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