Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS

Sun, Lei; Yang, Kun; Zhang, Liang; Qi, Li-ming; Chen, Jiamin; Li, Ping; Xiao, Jing; Zhao, Hongxin; Wang, Peng

doi:10.1186/s12981-020-00315-x

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…Altogether, this shows that productively infected cells become more exhausted as infection progresses. Previous studies have indeed shown that PD-1 or TIGIT expression correlates with the CD4 count in total CD4+ T cells [ 31 – 33 ]. This increased exhausted state could result from the repeated stimulations of these cells by the time of the latest HIV stages.…”

Section: Discussionmentioning

confidence: 95%

“…Second, immune exhaustion and activation during HIV infection have been well documented [ 30 ]. As an example, expression of immune checkpoint molecules PD-1 and TIGIT on CD4+ T cells was shown to increase with time during untreated infection [ 31 , 32 ] and was inversely correlated with the CD4+ T-cell count during AIDS [ 33 ]. CD4+ T cells from people with AIDS show the highest level of activation when compared to non-AIDS participants [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

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HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS

Faua,

Ursenbach,

Fuchs

et al. 2024

PAI

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Background: Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infected cells can help understand HIV production during this terminal stage. Methods: Blood samples from 15 untreated viremic participants (recent infection, n=5; long-term infection, n=5; active opportunistic AIDS-defining disease, n=5) and 5 participants virologically controlled on antiretroviral therapy (ART) enrolled in the Analysis of the Persistence, Reservoir and HIV Latency (APRIL) study (NCT05752318) were analyzed. Cells expressing the capsid protein p24 (p24+ cells) after 18 hours of resting or 24 hours of stimulation (HIV-Flow) revealed productively infected cells from viremic participants or translation-competent reservoir cells from treated participants, respectively. Results: The frequency of productively infected cells tended to be higher during AIDS in comparison with recent and long-term infections (median, 340, 72, and 32/million CD4+ T cells, respectively) and correlated with the plasma viral load at all stages of infection. Altogether, these cells were more frequently CD4low, HLA-ABClow, CD45RA-, Ki67+, PD-1+, with a non-negligible contribution from pTfh (CXCR5+PD-1+) cells, and were not significantly enriched in HIV coreceptors CCR5 nor CXCR4 expression. The comparison markers expression between stages showed that productively infected cells during AIDS were enriched in memory and exhausted cells. In contrast, the frequencies of infected pTfh were lower during AIDS compared to non-AIDS stages. A UMAP analysis revealed that total CD4+ T cells were grouped in 7 clusters and that productive p24+ cells were skewed to given clusters throughout the course of infection. Overall, the preferential targets of HIV during the latest stages seemed to be more frequently highly differentiated (memory, TTD-like) and exhausted cells and less frequently pTfh-like cells. In contrast, translation-competent reservoir cells were less frequent (5/million CD4+ T cells) and expressed more frequently HLA-ABC and less frequently PD-1. Conclusions: In long-term infection and AIDS, productively infected cells were differentiated and exhausted. This could indicate that cells with these given features are responsible for HIV production and dissemination in an immune dysfunction environment occurring during the last stages of infection.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS

Faua,

Ursenbach,

Fuchs

et al. 2024

PAI

View full text Add to dashboard Cite

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Mucosal T-cell responses to chronic viral infections: Implications for vaccine design

Al-Talib,

Dimonte,

Humphreys

2024

Cell Mol Immunol

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Mucosal surfaces that line the respiratory, gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment. Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses. Numerous pathogenic viruses, including herpesviruses and retroviruses, exploit this environment to establish chronic infection. Effector and regulatory T-cell populations, including effector and resident memory T cells, play instrumental roles in mediating the transition from acute to chronic infection, where a degree of viral replication is tolerated to minimize immunopathology. Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses. In this review, we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa. We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies: not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.

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Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS

Cited by 2 publications

References 24 publications

HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS

HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS

Mucosal T-cell responses to chronic viral infections: Implications for vaccine design

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