Massive CD8 T Cell Response to Primary HIV Infection in the Setting of Severe Clinical Presentation

Arnoczy, Gretchen; Ferrari, Guido; Goonetilleke, Nilu; Corrah, Tumena; Li, Hui; Kuruc, JoAnn; Schmitz, John L.; McGee, Kara; Hicks, Charles B.; Eron, Joseph J.; Ai, Aids Vaccine Immunology

doi:10.1089/aid.2011.0145

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…The current Research Topic includes in total 11 high-quality manuscripts, ranging from host-response activation during HIV infection (Tjitro et al While it is known that HIV infection is characterized by a dramatic depletion of CD4 + T cells, a study comparing people with HIV (PWH) with age-matched uninfected controls identified specifically gamma delta (γδ)-T cells as an inflammatory driver in ART-suppressed PWH and provided evidence of distinct "inflamm-aging" processes with and without active HIV replication (Belkina et al). Depletion of CD4 + T cells together with impaired polarization of Th17 cells in the gastrointestinal tract and a massive expansion of activated CD8 + T cells causes CD8 + T cell-mediated enteropathy (6). In another study of this Research Topic authors also reported dysbiosis and translocation of microbial products in the study participants, which persisted despite long term ART mediated viral suppression (Rhoades et al).…”

Section: Hiv-associated Immune Activation and Persistent Inflammationmentioning

confidence: 95%

Editorial: HIV-Associated Immune Activation and Persistent Inflammation

2019

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Section: Hiv-associated Immune Activation and Persistent Inflammationmentioning

confidence: 95%

Editorial: HIV-Associated Immune Activation and Persistent Inflammation

2019

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“…Studies in the simian immunodeficiency virus (SIV) model suggested that viral load decline after ART initiation during chronic SIV infection was independent from CD8 + T cell-mediated killing of SIVinfected cells (13,14). HIV-specific CD8 + T cells are induced at the early stage of infection at high numbers, and the magnitude and survival capacity of these responses in acute infection have been associated with a lower viral load set point (15)(16)(17)(18). Although the emergence of HIV-specific CD8 + T cells has been temporally associated with viral load decline in the absence of treatment (5,7,8), no study has yet reported a direct correlation between these responses and viral load decline.…”

Section: Introductionmentioning

confidence: 99%

Delayed differentiation of potent effector CD8 ⁺ T cells reducing viremia and reservoir seeding in acute HIV infection

et al. 2017

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CD8+ T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The SIV model provided the proof of concept for a CD8+ T cell-mediated reservoir clearance but showed conflicting evidences on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8+ T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. Here we studied HIV-specific CD8+ T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8+ T cells generated as early as AHI stage 1 and 2 prior to peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8+ T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Importantly, their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8+ T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8+ T cells contribute to reducing the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design of interventions aiming at inducing these potent responses to cure HIV infection.

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“…CD4 + T cells trigger many elements of the immune response, including regulation of CD8 + T cell activation ( 1 ). Early HIV infection is characterized by a dramatic depletion of CD4 + T cells and impaired polarization of Th17 cells in the gastrointestinal tract and a massive expansion of activated CD8 + T cells causing CD8 + T cell-mediated enteropathy ( 2 – 4 ), which is also characterized by microbial overgrowth and translocation of microbial products, including bacteria, fungi, and viruses, from the gut into the systemic circulation ( 5 ). Lactobacillales influence gut mucosal immunity by increasing the suppressive function of CD4 + regulatory T cells of colon lamina propria, which can alleviate HIV-associated colitis ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

(1→3)-β-d-Glucan: A Biomarker for Microbial Translocation in Individuals with Acute or Early HIV Infection?

et al. 2016

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BackgroundThe extent of gut microbial translocation, which plays roles in HIV disease progression and non-AIDS comorbidities, appears to vary with the composition of the gut microbiome, particularly the presence of Lactobacillales, which reduce mucosal injury. While low proportions of Lactobacillales in the distal gut microbiome are a very promising indicator of microbial translocation, measurement is expensive and complicated and not feasible for clinical routine. (1→3)-β-d-Glucan (BDG) is a component of most fungal cell walls and might be a surrogate marker for Lactobacillales proportion in the gut and a useful indicator of HIV-associated gut injury. This study evaluated BDG as a biomarker of gut integrity in adults with acute or early HIV infection (AEH).MethodsStudy samples were collected longitudinally during study visits at weeks 0, 12, and 24 in a cohort of 11 HIV-infected men starting antiretroviral therapy during AEH. Blood plasma levels of BDG, soluble cluster of differentiation 14 (sCD14) and lipopolysaccharide (LPS) were measured and then correlated with the proportion of Lactobacillales in the distal gut microbiome, as measured by 16s rDNA sequencing by using mixed-effects models with random intercepts.ResultsMean BDG and sCD14 levels across subjects were associated with Lactobacillales after controlling for time effects and within-subjects correlations (p-values < 0.05), while LPS levels were not. Specifically, each point increase in mean BDG and sCD14 levels across participants was associated with 0.31 ± 0.14 and 0.03 ± 0.01 percent decrease in mean Lactobacillales proportions, respectively.ConclusionBDG and sCD14 may be indicators of low Lactobacillales in the gut in adults with acute or early HIV infection, and serve as biomarkers of gut integrity and microbial translocation in HIV infection. Larger studies are needed to confirm our findings.

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Massive CD8 T Cell Response to Primary HIV Infection in the Setting of Severe Clinical Presentation

Cited by 4 publications

References 17 publications

Editorial: HIV-Associated Immune Activation and Persistent Inflammation

Editorial: HIV-Associated Immune Activation and Persistent Inflammation

Delayed differentiation of potent effector CD8 ⁺ T cells reducing viremia and reservoir seeding in acute HIV infection

(1→3)-β-d-Glucan: A Biomarker for Microbial Translocation in Individuals with Acute or Early HIV Infection?

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Massive CD8 T Cell Response to Primary HIV Infection in the Setting of Severe Clinical Presentation

Cited by 4 publications

References 17 publications

Editorial: HIV-Associated Immune Activation and Persistent Inflammation

Editorial: HIV-Associated Immune Activation and Persistent Inflammation

Delayed differentiation of potent effector CD8 + T cells reducing viremia and reservoir seeding in acute HIV infection

(1→3)-β-d-Glucan: A Biomarker for Microbial Translocation in Individuals with Acute or Early HIV Infection?

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Delayed differentiation of potent effector CD8 ⁺ T cells reducing viremia and reservoir seeding in acute HIV infection