IL-12-Induced Immune Suppressive Deficit During CD8+ T-Cell Differentiation

Pranav S Renavikar; Sushmita Sinha; Ashley A Brate; Nicholas Borcherding; Michael P Crawford; Scott M Steward-Tharp; Nitin J Karandikar

doi:10.3389/fimmu.2020.568630

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IL-12-Induced Immune Suppressive Deficit During CD8+ T-Cell Differentiation

Journal article

Open access

Peer reviewed

IL-12-Induced Immune Suppressive Deficit During CD8+ T-Cell Differentiation

Pranav S Renavikar, Sushmita Sinha, Ashley A Brate, Nicholas Borcherding, Michael P Crawford, Scott M Steward-Tharp and Nitin J Karandikar

Frontiers in immunology, Vol.11, pp.568630-568630

2020

DOI: 10.3389/fimmu.2020.568630

PMCID: PMC7657266

PMID: 33193343

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https://doi.org/10.3389/fimmu.2020.568630View

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Abstract

Autoimmune diseases are characterized by regulatory deficit in both the CD4+ and CD8+ T-cell compartments. We have shown that CD8+ T-cells associated with acute relapse of multiple sclerosis are significantly deficient in their immune suppressive ability. We hypothesized that distinct CD8+ cytotoxic T-cell (Tc) lineages, determined by cytokine milieu during naïve T-cell differentiation, may harbor differential ability to suppress effector CD4+ T-cells. We differentiated purified human naïve CD8+ T-cells toward Tc0 (media control), Tc1 and Tc17 lineages. Using flow cytometric suppression assays, we observed that Tc0 and Tc17 cells had similar suppressive ability. In contrast, Tc1 cells showed significant loss of suppressive ability against CD4+ T-cells and -differentiated Th0, Th1 and Th17 cells. Of note, Tc1 cells were also suboptimal in suppressing CD4-induced acute xenogeneic graft versus host disease (xGVHD) . Tc subtypes derived under various cytokine combinations revealed that IL-12-containing conditions resulted in less suppressive cells exhibiting dysregulated cytotoxic degranulation. RNA sequencing transcriptome analyses indicated differential regulation of inflammatory genes and enrichment in GM-CSF-associated pathways. These studies provide insights into the role of T-cell differentiation in CD8 suppressive biology and may reveal therapeutically targetable pathways to reverse suppressive deficit during immune-mediated disease.

Animals

CD4-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - immunology

Cell Differentiation

Female

Graft vs Host Disease - immunology

Humans

Immune Tolerance

Interleukin-12 - immunology

Mice

Details

Title: Subtitle: IL-12-Induced Immune Suppressive Deficit During CD8+ T-Cell Differentiation
Creators: Pranav S Renavikar - University of Iowa
Sushmita Sinha - University of Iowa
Ashley A Brate - University of Iowa
Nicholas Borcherding - University of Iowa
Michael P Crawford - University of Iowa
Scott M Steward-Tharp - University of Iowa Health Care
Nitin J Karandikar - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.11, pp.568630-568630
DOI: 10.3389/fimmu.2020.568630
PMID: 33193343
PMCID: PMC7657266
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Grant note: R01 AI121567 / NIAID NIH HHS T90 DE023520 / NIDCR NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 2020
Academic Unit: Dermatology; Oral Pathology, Radiology and Medicine; Pathology; Dental Research
Record Identifier: 9984186573002771

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