Induction of regulatory T-cells from memory T-cells is perturbed during acute exacerbation of multiple sclerosis

Imran H Mohiuddin; Vinodh Pillai; Ethan J Baughman; Benjamin M Greenberg; Elliot M Frohman; Michael P Crawford; Sushmita Sinha; Nitin J Karandikar

doi:10.1016/j.clim.2016.05.001

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Induction of regulatory T-cells from memory T-cells is perturbed during acute exacerbation of multiple sclerosis

Journal article

Open access

Peer reviewed

Induction of regulatory T-cells from memory T-cells is perturbed during acute exacerbation of multiple sclerosis

Imran H Mohiuddin, Vinodh Pillai, Ethan J Baughman, Benjamin M Greenberg, Elliot M Frohman, Michael P Crawford, Sushmita Sinha and Nitin J Karandikar

Clinical immunology (Orlando, Fla.), Vol.166-167, pp.12-18

05/2016

DOI: 10.1016/j.clim.2016.05.001

PMCID: PMC4902765

PMID: 27154631

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Abstract

Regulatory T-cells (Tregs) are vital for maintaining immunological self-tolerance, and the transcription factor FOXP3 is considered critical for their development and function. Peripheral Treg induction may significantly contribute to the total Treg pool in healthy adults, and this pathway may be enhanced in thymic-deficient conditions like multiple sclerosis (MS). Here, we evaluated iTreg formation from memory versus naïve CD4+CD25− T-cell precursors. We report the novel finding that memory T-cells readily expressed CD25 and FOXP3, and demonstrated significantly greater suppressive function. Additionally, the CD25−FOXP3− fraction of stimulated memory T-cells also displayed robust suppression not observed in naïve counterparts or ex vivo resting (CD25−) T-cells. This regulatory population was present in both healthy subjects and clinically-quiescent MS patients, but was specifically deficient during disease exacerbation. These studies indicate that iTreg development and function are precursor dependent. Furthermore, MS quiescence appears to correlate with restoration of suppressive function in memory-derived CD4+CD25−FOXP3− iTregs. •Memory (but not naïve) CD4+CD25- T-cells have greater capacity to generate iTregs.•Memory-derived CD4+CD25-FOXP3- T-cells also possess suppressive ability.•Memory-derived CD4+CD25-FOXP3- iTregs are deficient during acute relapse of MS.

Naïve

Multiple sclerosis

Immune regulation

T cells

FOXP3

Memory

Details

Title: Subtitle: Induction of regulatory T-cells from memory T-cells is perturbed during acute exacerbation of multiple sclerosis
Creators: Imran H Mohiuddin - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Vinodh Pillai - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Ethan J Baughman - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Benjamin M Greenberg - Department of Neurology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Elliot M Frohman - Department of Neurology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Michael P Crawford - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242, USA
Sushmita Sinha - Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242, USA
Nitin J Karandikar - Department of Pathology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
Resource Type: Journal article
Publication Details: Clinical immunology (Orlando, Fla.), Vol.166-167, pp.12-18
DOI: 10.1016/j.clim.2016.05.001
PMID: 27154631
PMCID: PMC4902765
NLM abbreviation: Clin Immunol
ISSN: 1521-6616
eISSN: 1521-7035
Publisher: Elsevier Inc
Grant note: name: NIH, award: K24AI079272; DOI: 10.13039/100000890, name: National MS Society, award: RG4922A3/T
Language: English
Date published: 05/2016
Academic Unit: Pathology
Record Identifier: 9984046803602771

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