Document Type

Article

Publication Date

3-17-2021

Publication Title

Front Immunol

Keywords

JGM

JAX Source

Front Immunol 2021 Mar 17; 12:636720

Volume

12

First Page

636720

Last Page

636720

ISSN

1664-3224

PMID

33815388

DOI

https://doi.org/10.3389/fimmu.2021.636720

Abstract

Immune cell activation assays have been widely used for immune monitoring and for understanding disease mechanisms. However, these assays are typically limited in scope. A holistic study of circulating immune cell responses to different activators is lacking. Here we developed a cost-effective high-throughput multiplexed single-cell RNA-seq combined with epitope tagging (CITE-seq) to determine how classic activators of T cells (anti-CD3 coupled with anti-CD28) or monocytes (LPS) alter the cell composition and transcriptional profiles of peripheral blood mononuclear cells (PBMCs) from healthy human donors. Anti-CD3/CD28 treatment activated all classes of lymphocytes either directly (T cells) or indirectly (B and NK cells) but reduced monocyte numbers. Activated T and NK cells expressed senescence and effector molecules, whereas activated B cells transcriptionally resembled autoimmune disease- or age-associated B cells (e.g., CD11c, T-bet). In contrast, LPS specifically targeted monocytes and induced two main states: early activation characterized by the expression of chemoattractants and a later pro-inflammatory state characterized by expression of effector molecules. These data provide a foundation for future immune activation studies with single cell technologies (https://czi-pbmc-cite-seq.jax.org/).

Comments

We thank all members of the Stitzel and Ucar labs for constructive feedback and discussion on this study and manuscript. We also thank members of the Human Cell Atlas data wrangler team for assistance with depositing the data associated with this manuscript.

This is an open-access article distributed under the terms of the Creative Commons Attribution License.

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