Effector and regulatory functions of vaccine-induced memory T cells in human tissues

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B903
Abstract ID: 4464

Presenting Author:
Julia Davis-Porada , Graduate Student at Columbia Univ.

Abstract:

The ability of vaccines to induce memory and protective immunity is largely correlated with circulating antibodies, while the functional capacity and distribution of memory T cells maintained in tissues is unknown. Here, we profiled the surface proteome, transcriptome, and T cell receptor repertoire using CITE-seq of vaccine-induced SARS-CoV-2 Spike (S) protein- and Influenza (flu)-specific memory T cells, isolated using the activation-induced marker assay across lymphoid and mucosal tissues from organ donors and blood from living participants. We identified heterogeneous functional T cell programs for S- and flu-specific CD4 T cells including Th1/Th2/Th17 cytokine production, proliferation, interferon responses, and subsets of activated regulatory T cells (Tregs) along with cytotoxic and effector CD8 T cell profiles. Overall, clonal expansion was greatest in CD8 T cells and in CD4 Tregs; overlap across tissues was mostly found for CD8 T cells in blood rich sites (e.g., lung, spleen, and bone marrow). Interestingly, S-specific T expanded clones were mostly within the Treg subset, while flu-specific expanded clones were CD8 effector T cells. Moreover, S-specific Tregs were more prevalent within lymphoid tissues than in blood. Our results reveal that vaccines and infections generate memory in tissues with both effector and regulatory functional capacity, suggesting the ability to control recall responses to pathogens may constitute an important aspect of the protective profile.