The Proteomic Landscape of Resting and Activated CD4+ T Cells Reveal Insights into Cell Differentiation and Function

Abstract

CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out a label-free high-resolution FTMS-based proteomic profiling of resting and T cell receptor-activated (72 h) primary human CD4+ T cells from peripheral blood of healthy donors as well as SUP-T1 cells. We identified 5237 proteins, of which significant alterations in the levels of 1119 proteins were observed between resting and activated CD4+ T cells. In addition to identifying several known T-cell activation-related processes altered expression of several stimulatory/inhibitory immune checkpoint markers between resting and activated CD4+ T cells were observed. Network analysis further revealed several known and novel regulatory hubs of CD4+ T cell activation, including IFNG, IRF1, FOXP3, AURKA, and RIOK2. Comparison of primary CD4+ T cell proteomic profiles with human lymphoblastic cell lines revealed a substantial overlap, while comparison with mouse CD+ T cell data suggested interspecies proteomic differences. The current dataset will serve as a valuable resource to the scientific community to compare and analyze the CD4+ proteome.

ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells

“…Primary resting CD4 T cells displayed low expression levels of all Arp2/3 complex subunits, but T cell activation increased their levels significantly. This induction of protein levels by T cell activation was paralleled by induction of mRNA expression assessed by qRT-PCR ( Figure 2—figure supplement 1A : absolute values; Figure 2—figure supplement 1B : relative to GAPDH; note that equal number of cells was loaded and that housekeeping genes are also subject to regulation by T cell activation; Roy et al, 2020 ; Sousa et al, 2019 ; Subbannayya et al, 2020 ).…”

Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC

“…Opposing to the infiltrations of CD8+ cells and DCs, increased infiltration of CD4+ T helper cells, including Th1 and Th2 cells, and B cell progenitors (pro B) were significantly associated with worse patient survival and higher 11LNCPS scores in HCC ( Figures 3A, B ). Th1 and Th2 cells play important immunoregulatory roles in adaptive immunity, including the activation of B cells and cytotoxic T cells ( 69 , 70 ). but their role in HCC development is not well understood ( 71 ).…”

Temporal Quantitative Phosphoproteomics Profiling of Interleukin-33 Signaling Network Reveals Unique Modulators of Monocyte Activation

“…Hypergeometric enrichment-based pathway analyses were carried out as described previously [ 26 ]. Briefly, R (R studio v. 1.3.1073, R v. 4.0.2, Bioconductor v. 3.11.1) scripts using clusterProfiler (v. 3.16.1) [ 27 ] and Reactome pathways [ 28 ] using the Reactome package (v. 1.32.0) [ 29 ] were used for the analyses.…”