Format

Send to

Choose Destination
Cells. 2019 Aug 10;8(8). pii: E871. doi: 10.3390/cells8080871.

The Abnormal CD4+T Lymphocyte Subset Distribution and Vbeta Repertoire in New-onset Rheumatoid Arthritis Can Be Modulated by Methotrexate Treament.

Author information

1
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
2
Department of Medicine, University Hospital "Príncipe de Asturias", University of Alcalá and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Alcalá de Henares, 28871 Madrid, Spain.
3
Immune System Diseases-Rheumatology Service, University Hospital "Príncipe de Asturias", Alcalá de Henares, 28871 Madrid, Spain.
4
Division of Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA 30322, USA.
5
Laboratory of Immune System Diseases, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain. mademons@gmail.com.
6
Department of Medicine, University Hospital "Príncipe de Asturias", University of Alcalá and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Alcalá de Henares, 28871 Madrid, Spain. mademons@gmail.com.
7
Immune System Diseases-Rheumatology Service, University Hospital "Príncipe de Asturias", Alcalá de Henares, 28871 Madrid, Spain. mademons@gmail.com.

Abstract

Patients with long-term, treated, rheumatoid arthritis (RA) show abnormalities in their circulating CD4+ T-lymphocytes, but whether this occurs in recently diagnosed naïve patients to disease-modifying drugs (DMARDs) is under discussion. These patients show heterogeneous clinical response to methotrexate (MTX) treatment. We have examined the count of circulating CD4+ T-lymphocytes, and their naïve (TN), central memory (TCM), effector memory (TEM) and effector (TE) subsets, CD28 expression and Vβ TCR repertoire distribution by polychromatic flow cytometry in a population of 68 DMARD-naïve recently diagnosed RA patients, before and after 3 and 6 months of MTX treatment. At pre-treatment baseline, patients showed an expansion of the counts of CD4+ TN, TEM, TE and TCM lymphocyte subsets, and of total CD4+CD28- cells and of the TE subset with a different pattern of numbers in MTX responder and non-responders. The expansion of CD4+TEM lymphocytes showed a predictive value of MTX non-response. MTX treatment was associated to different modifications in the counts of the CD4+ subsets and of the Vβ TCR repertoire family distribution and in the level of CD28 expression in responders and non-responders. In conclusion, the disturbance of CD4+ lymphocytes is already found in DMARD-naïve RA patients with different patterns of alterations in MTX responders and non-responders.

KEYWORDS:

CD4+ T lymphocytes; TCR Vb; flow cytometry; methotrexate; rheumatoid arthritis

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center