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Older kidney transplant recipients demonstrate increased rates of infection, and lower rates of rejection, compared with younger kidney transplant recipients. However, the mechanism behind this observation remains unknown. To develop a multifaceted view of age-associated immune dysfunction, we determined the function and phenotype of T cells predisposing to vulnerability to infection on a molecular level. Overlapping peptide pools representing the dominant CMV antigens were used to stimulate PBMC collected from 51 kidney transplant recipients, using cytokine secretion to determine specificity and intensity of response. Staphylococcal endotoxin B (SEB) was analyzed in parallel. To define immune cell subsets, we used single cell RNA sequencing (scRNAseq) to evaluate cellular surface markers and gene expression. We found increased frequency of SEB- and CMV-specific T cells was associated with freedom from infection, especially in older patients. Spatialized t-SNE analysis revealed decreased frequency of naïve T cells, increased frequency of TEMRA cells, and decreased frequency of IFNγ secreting T cells in patients with infection. Application of scRNAseq analysis revealed increased frequency of terminally differentiated T cells expressing NK-associated receptors and inhibitory markers. These findings offer unique insight into the mechanism behind vulnerability to infection in the kidney transplant recipient, revealing a specific T cell subtype of impaired antigen response and terminal effector phenotype as markers of T cell senescence. [ABSTRACT FROM AUTHOR]

• In Vanuatu, ocular Chlamydia infection prevalence is low; in Kiribati it is high. • In Vanuatu, Pgp3 seroprevalence does not increase in childhood; in Kiribati it does. • Conjunctival scarring is more common in adults in Kiribati than in Vanuatu. • Trachomatous inflammation—follicular lacks specificity for ocular Chlamydia infection. • Non-TF markers may help to determine need for interventions against active trachoma. In the peri-elimination setting, the positive predictive value of trachomatous inflammation–follicular (TF), the primary marker used to determine need for antibiotics for trachoma, is suboptimal. Here, three non-TF measures are used to compare two regions where TF prevalence exceeds the threshold for intervention, but where the Chlamydia trachomatis (Ct) prevalence is different. Population prevalence of trachoma was measured in Vanuatu (n = 3470) and Kiribati (n = 2922). Dried blood spots (DBS) and conjunctival photographs were collected from every survey participant, and conjunctival swabs were collected from those aged 1–9 years. Individuals were tested for blood anti-Pgp3 antibodies, Ct DNA at the conjunctiva and severity of conjunctival scarring. The prevalence of TF in 1–9-year-olds was 16.5% in Vanuatu and 38.2% in Tarawa. 7% of people aged ≥1 year in Vanuatu had conjunctival scarring compared to 27% in Tarawa. The prevalence of ocular Ct infection in 1–9-year-olds was 1.5% in Vanuatu and 27.4% in Tarawa. The seroconversion rate amongst 1–9-year-old children in Vanuatu and Tarawa was 0.018 and 0.197 events per child per year, respectively. Comparing Vanuatu to Tarawa demonstrates several markers that could be used to differentiate the trachoma status of populations in these (and other) locations. [ABSTRACT FROM AUTHOR]

Class II HLA loci DRB1, DQB1 and DPB1 were typed for a total of 939 Gambian participants by locus-specific amplicon sequencing. Participants were from multiple regions of The Gambia and drawn from two studies: a family study aiming to identify associations between host genotype and trachomatous scarring (N = 796) and a cohort study aiming to identify correlates of immunity to trachoma (N = 143). All loci deviated from Hardy-Weinberg equilibrium, likely due to the family-based nature of the study: 608 participants had at least one other family member included in the study population. The most common alleles for HLA-DRB1, DQB1 and DPB1 respectively were DRB1*13:04 (18.8 %), DQB1*03:19 (27.9 %) and DPB1*01:01 (25.4 %). Participants belonged to a variety of ethnicities, including the Mandinka, Fula, Wolof and Jola ethnic groups. [ABSTRACT FROM AUTHOR]