Increased PD-1+CD154+ Tfh cells are possibly the most important functional subset of PD-1+ T follicular helper cells in adult patients with minimal change disease

Tao Li; Yunpeng Shi; Weixia Sun; Haifeng Wang; Quan Wang; Yanfang Jiang

doi:10.1016/j.molimm.2017.12.020

Increased PD-1⁺CD154⁺ Tfh cells are possibly the most important functional subset of PD-1⁺ T follicular helper cells in adult patients with minimal change disease

Mol Immunol. 2018 Feb:94:98-106. doi: 10.1016/j.molimm.2017.12.020. Epub 2017 Dec 27.

Authors

Tao Li¹, Yunpeng Shi², Weixia Sun³, Haifeng Wang⁴, Quan Wang⁵, Yanfang Jiang⁶

Affiliations

¹ Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China. Electronic address: [email protected].
² Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China. Electronic address: [email protected].
³ Department of Nephrology, The First Hospital of Jilin University, Changchun, 130021, China. Electronic address: [email protected].
⁴ Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China. Electronic address: [email protected].
⁵ Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China. Electronic address: [email protected].
⁶ Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China; Key Laboratory of Zoonoses Research, Ministry of Education, The First Hospital of Jilin University, Changchun, 130021, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. Electronic address: [email protected].

PMID: 29288900
DOI: 10.1016/j.molimm.2017.12.020

Abstract

T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1)⁺ Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1⁺ Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1⁺, PD-1⁺CD154⁺, and PD-1⁺interleukin (IL)-21⁺ Tfh cells, and CD38⁺CD19⁺ and CD38⁺CD19⁺CD40⁺ B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0.05). However, no significant difference was found in PD-1⁺BCL-6⁺ or PD-1⁺ICOS⁺ Tfh cells. Furthermore, the percentages of PD-1⁺ Tfh and PD-1⁺CD154⁺ Tfh cells were negatively correlated with the estimated glomerular filtration rate (eGFR), but positively correlated with the 24-h urinary protein concentration and serum IL-21 level. The percentages of PD-1⁺ Tfh and PD-1⁺CD154⁺ Tfh cells were positively correlated with the percentages of CD38⁺ plasma cells and active CD38⁺CD40⁺ plasma cells, respectively. After an 8-12-week treatment with prednisolone, the percentages of PD-1⁺, PD-1⁺CD154⁺, and PD-1⁺IL-21⁺ Tfh cells as well as the serum level of IL-21 were significantly reduced; in contrast, the serum levels of IL-4 and IL-10 were increased (P < 0.05). We conclude that increased PD-1⁺CD154⁺ Tfh cells are possibly the most important functional subset of PD-1⁺ Tfh cells and may contribute towards the pathogenesis of MCD.

Keywords: CD154; Minimal change disease; PD-1; Tfh cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
CD40 Ligand / metabolism*
Case-Control Studies
Female
Humans
Lymphocyte Count
Male
Middle Aged
Nephrosis, Lipoid / immunology*
Nephrosis, Lipoid / metabolism
Nephrosis, Lipoid / pathology
Programmed Cell Death 1 Receptor / metabolism*
T-Lymphocyte Subsets / metabolism
T-Lymphocyte Subsets / pathology*
T-Lymphocytes, Helper-Inducer / metabolism
T-Lymphocytes, Helper-Inducer / pathology*
Young Adult

Substances

PDCD1 protein, human
Programmed Cell Death 1 Receptor
CD40 Ligand