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Multilevel human secondary lymphoid immune system compartmentalization revealed by complementary imaging approaches.

ABSTRACT: Secondary human lymphoid tissue immune reactions take place in a highly coordinated environment with compartmentalization representing a fundamental feature of this organization. In situ profiling methodologies are indispensable for the understanding of this compartmentalization. Here, we propose a complementary experimental approach aiming to reveal different aspects of this process. The analysis of human tonsils, using a combination of single cell phenotypic analysis based on flow cytometry and multiplex imaging and mass spectrometry-based methodologies, revealed a compartmentalized organization at the cellular and molecular levels. More specifically, the skewed distribution of highly specialized immune cell subsets and relevant soluble mediators was accompanied by a compartmentalized localization of several lipids across different anatomical areas of the tonsillar tissue. The performance of such combinatorial experimental approaches could lead to the identification of novel in situ interactions and molecular targets for the in vivo manipulation of lymphoid organ, particularly the germinal center, immune reactions.

SUBMITTER: Oyler BL

PROVIDER: S-EPMC10371825 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Multilevel human secondary lymphoid immune system compartmentalization revealed by complementary imaging approaches.

Oyler Benjamin L BL Valencia-Dávila Jeferson A JA Moysi Eirini E Molyvdas Adam A Ioannidou Kalliopi K March Kylie K Ambrozak David D De Leval Laurence L Fabozzi Giulia G Woods Amina S AS Koup Richard A RA Petrovas Constantinos C

iScience 20230703 8

Secondary human lymphoid tissue immune reactions take place in a highly coordinated environment with compartmentalization representing a fundamental feature of this organization. <i>In situ</i> profiling methodologies are indispensable for the understanding of this compartmentalization. Here, we propose a complementary experimental approach aiming to reveal different aspects of this process. The analysis of human tonsils, using a combination of single cell phenotypic analysis based on flow cytom ...[more]

PMID: 37520703

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Project description:The reproducible nature of HIV-1 escape from HLA-restricted CD8+ T-cell responses allows the identification of HLA-associated viral polymorphisms "at the population level" - that is, via analysis of cross-sectional, linked HLA/HIV-1 genotypes by statistical association. However, elucidating their timing of selection traditionally requires detailed longitudinal studies, which are challenging to undertake on a large scale. We investigate whether the extent and relative timecourse of immune-driven HIV adaptation can be inferred via comparative cross-sectional analysis of independent early and chronic infection cohorts.Similarly-powered datasets of linked HLA/HIV-1 genotypes from individuals with early (median?<?3 months) and chronic untreated HIV-1 subtype B infection, matched for size (N?>?200/dataset), HLA class I and HIV-1 Gag/Pol/Nef diversity, were established. These datasets were first used to define a list of 162 known HLA-associated polymorphisms detectable at the population level in cohorts of the present size and host/viral genetic composition. Of these 162 known HLA-associated polymorphisms, 15% (occurring at 14 Gag, Pol and Nef codons) were already detectable via statistical association in the early infection dataset at p???0.01 (q?<?0.2) - identifying them as the most consistently rapidly escaping sites in HIV-1. Among these were known rapidly-escaping sites (e.g. B*57-Gag-T242N) and others not previously appreciated to be reproducibly rapidly selected (e.g. A*31:01-associated adaptations at Gag codons 397, 401 and 403). Escape prevalence in early infection correlated strongly with first-year escape rates (Pearson's R?=?0.68, p?=?0.0001), supporting cross-sectional parameters as reliable indicators of longitudinally-derived measures. Comparative analysis of early and chronic datasets revealed that, on average, the prevalence of HLA-associated polymorphisms more than doubles between these two infection stages in persons harboring the relevant HLA (p?<?0.0001, consistent with frequent and reproducible escape), but remains relatively stable in persons lacking the HLA (p?=?0.15, consistent with slow reversion). Published HLA-specific Hazard Ratios for progression to AIDS correlated positively with average escape prevalence in early infection (Pearson's R?=?0.53, p?=?0.028), consistent with high early within-host HIV-1 adaptation (via rapid escape and/or frequent polymorphism transmission) as a correlate of progression.Cross-sectional host/viral genotype datasets represent an underutilized resource to identify reproducible early pathways of HIV-1 adaptation and identify correlates of protective immunity.

Dataset Information

Multilevel human secondary lymphoid immune system compartmentalization revealed by complementary imaging approaches.

Publications

Multilevel human secondary lymphoid immune system compartmentalization revealed by complementary imaging approaches.

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