Spatial Characterization of the Immune Microenvironment within HIV+ Lymph Nodes

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B536
Abstract ID: 5113

Presenting Author:
Robert L. Furler O'Brien , Assistant Professor of Immunology at Weill Cornell Med.

Abstract:

Background: Persistent HIV replication is hypothesized to induce chronic inflammation in ART-suppressed people living with HIV (PLWH), however defining this chronic inflammation within tissues is limited. Molecular and spatial characterization of chronic inflammation within human lymph nodes from PLWH provide valuable information on the immunological microenvironment that limits viral eradication.

Methods: We spatially characterized the transcriptomic and proteomic profiles of the lymph node microenvironment from 6 human lymph nodes: three from ART-suppressed PLWH, two from chronically infected PLWH, and one from a male HIV- control donor. For spatial transcriptomics analysis, lymph nodes were either from fresh-frozen or FFPE tissue. Lymph node sections (10μm) were placed onto the 10X Visium slides, stained with H&E, and imaged prior to RNA-Seq library prep. Following sequencing cluster identification was done with single cell RNA-seq datasets and downstream bioinformatics analyses were performed.

Results: Following the bioinformatic integration of spatial transcriptomic datasets, cluster analysis identified pro-inflammatory T cells within the HIV+ tissues compared to the HIV- tissue within the T cell zone.  Additionally, two sets of proinflammatory myeloid cells were identified that were spatially located within the afferent and efferent lymphatics in the HIV+ tissues.  These proinflammatory clusters further characterize chronic inflammation that occurs in PLWH.