People living with HIV (PLWH) who are immune nonresponders (INRs) are at greater risk of comorbidity and mortality than are immune responders (IRs) who restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low CD4+ T cell counts (<350 c/μL), heightened systemic inflammation, and increased CD4+ T cell cycling (Ki67+). Here, we report the findings that memory CD4+ T cells and plasma samples of INRs from several cohorts are enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) that both negatively correlated with CD4+ T cell counts. In vitro PCS or IS blocked CD4+ T cell proliferation, induced apoptosis, and diminished the expression of mitochondrial proteins. Electron microscopy imaging revealed perturbations of mitochondrial networks similar to those found in INRs following incubation of healthy memory CD4+ T cells with PCS. Using bacterial 16S rDNA, INR stool samples were found enriched in proteolytic bacterial genera that metabolize tyrosine and phenylalanine to produce PCS. We propose that toxic solutes from the gut bacterial flora may impair CD4+ T cell recovery during ART and may contribute to CD4+ T cell lymphopenia characteristic of INRs.
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http://dx.doi.org/10.1172/JCI149571 | DOI Listing |
Sci Adv
January 2025
Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore", IEOS-CNR, Napoli, Italy.
CD4FOXP3 regulatory T cells (T) suppress immune responses to tumors, and their accumulation in the tumor microenvironment (TME) correlates with poor clinical outcome in several cancers, including breast cancer (BC). However, the properties of intratumoral T remain largely unknown. Here, we found that a functionally distinct subpopulation of T, expressing the FOXP3 Exon2 splicing variants, is prominent in patients with hormone receptor-positive BC with poor prognosis.
View Article and Find Full Text PDFAIDS
January 2025
Botswana Harvard Health Partnership, 1836 Northring Road, Gaborone, Botswana.
Objective: To evaluate the impact of ART duration and CD4 count on risk for high grade cervical dysplasia in women with HIV (WWH) compared to women without HIV in the treat-all era with integrase strand inhibitors (INSTIs).
Design: Prospective longitudinal cohort study in Botswana.
Methods: From February 2021 to August 2022, baseline HPV self-sampling was offered to women with and without HIV.
Clin Rheumatol
January 2025
Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Previous research has demonstrated ɑ7nAch receptor (ɑ7nAchR) agonists to provide benefit for rheumatoid arthritis (RA) patients. However, the immunological mechanism of action for these ɑ7nAchR agonists has not been elucidated. Herein, the effect of GTS-21, a selective ɑ7nAchR agonist, on the differentiation of Th17 and Th2 cells was assessed.
View Article and Find Full Text PDFInflamm Res
January 2025
Institute of Allergy and Clinical Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
Particulate matter (PM) exposure has been proposed as one of the causes of steroid resistance. However, studies investigating this using patient samples or animals are still lacking. Therefore, in this study, we aimed to investigate the changes in cytokines and mTOR (mammalian target of rapamycin) activation in patients with steroid resistant asthma and the role of mTOR in a mouse model of steroid resistant asthma induced by PM.
View Article and Find Full Text PDFJ Obstet Gynaecol Res
January 2025
Department of Obstetrics, HanDan Central Hospital, HanDan, China.
Objective: Abnormal levels and imbalances of T cell subsets are common in recurrent spontaneous abortion (RSA) patients, but most studies have small sample sizes, and comprehensive evaluations are lacking. Therefore, this meta-analysis aimed to comprehensively investigate T cell subsets and their ratios in RSA patients.
Methods: Four databases (PubMed, EMBASE, Web of Science, and Cochrane Library databases) were searched until 10 January 2024.
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