The Type of Responder T-cell Has a Significant Impact in a Human in Vitro Suppression Assay

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Dec 15

PMID 21151941

Citations 4

Authors

Srikanta Jana

Hope Campbell

Jeffrey Woodliff

Jill Waukau

Parthav Jailwala

Jugal Ghorai

Soumitra Ghosh

Sanja Glisic

Affiliations

Soon will be listed here.

Abstract

Background: In type 1 diabetes (T1D), a prototypic autoimmune disease, effector T cells destroy beta cells. Normally, CD4(+)CD25(+high), or natural regulatory T cells (Tregs), counter this assault. In autoimmunity, the failure to suppress CD4(+)CD25(low) T cells is important for disease development. However, both Treg dysfunction and hyperactive responder T-cell proliferation contribute to disease.

Methods/principal Findings: We investigated human CD4(+)CD25(low) T cells and compared them to CD4(+)CD25(-) T cells in otherwise equivalent in vitro proliferative conditions. We then asked whether these differences in suppression are exacerbated in T1D. In both single and co-culture with Tregs, the CD4(+)CD25(low) T cells divided more rapidly than CD4(+)CD25(-) T cells, which manifests as increased proliferation/reduced suppression. Time-course experiments showed that this difference could be explained by higher IL-2 production from CD4+CD25(low) compared to CD4+CD25- T cells. There was also a significant increase in CD4+CD25(low) T-cell proliferation compared to CD4+CD25- T cells during suppression assays from RO T1D and at-risk subjects (n = 28, p = 0.015 and p = 0.024 respectively).

Conclusions/significance: The in vitro dual suppression assays proposed here could highlight the impaired sensitivity of certain responder T cells to the suppressive effect of Tregs in human autoimmune diseases.

Citing Articles

Regulatory T cell dysfunction in type 1 diabetes: what's broken and how can we fix it?.

Hull C, Peakman M, Tree T Diabetologia. 2017; 60(10):1839-1850.

PMID: 28770318 PMC: 6448885. DOI: 10.1007/s00125-017-4377-1.

Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127(low) Treg Cells in Patients With Chronic Rheumatoid Arthritis.

Walter G, Fleskens V, Frederiksen K, Rajasekhar M, Menon B, Gerwien J Arthritis Rheumatol. 2015; 68(1):103-16.

PMID: 26314565 PMC: 4832388. DOI: 10.1002/art.39408.

Advances in the cellular immunological pathogenesis of type 1 diabetes.

Li M, Song L, Qin X J Cell Mol Med. 2014; 18(5):749-58.

PMID: 24629100 PMC: 4119381. DOI: 10.1111/jcmm.12270.

Efficient expansion of cryopreserved CD4(+)CD25(+)CD127(lo/-) cells in Type 1 diabetes.

Ryden A, Faresjo M Results Immunol. 2013; 1(1):36-44.

PMID: 24371551 PMC: 3787809. DOI: 10.1016/j.rinim.2011.08.001.

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