Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood
2011 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, no 1, 57-66 p.Article in journal (Refereed) Published
Background:Multiple sclerosis (MS) is hypothetically caused by autoreactive Th1 and Th17 cells, whereas Th2 and regulatory T cells may confer protection. The development of Th subpopulations is dependant on the expression of lineage-specific transcription factors.
Objective:The aim of this study was to assess the balance of CD4+T cell populations in relapsing-remitting MS.
Methods:Blood mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 was assessed in 33 patients with relapsing-remitting MS and 20 healthy controls. In addition, flow cytometry was performed to assess T lymphocyte numbers.
Results:In relapsing-remitting MS, diminished expression of FOXP3 (Treg) was found (p < 0.05), despite normal numbers of CD4+CD25hiTreg. Immunoregulatory EBI3 and Th2-associated GATA3 ([a-z]+) was also decreased in MS (p < 0.005 and p < 0.05, respectively). Expression of TBX21 (Th1) and RORC (Th17) did not differ between patients and controls. Similar changes were observed when analysing beta-interferon treated (n = 12) or untreated (n = 21) patients. Analysis of transcription factor ratios, comparing TBX21/GATA3 and RORC/FOXP3, revealed an increase in the RORC/FOXP3 ratio in patients with relapsing-remitting MS (p < 0.005).
Conclusion:Our findings indicate systemic defects at the mRNA level, involving downregulation of beneficial CD4+phenotypes. This might play a role in disease development by permitting activation of harmful T cell populations.
Place, publisher, year, edition, pages
Sage Publications, 2011. Vol. 17, no 1, 57-66 p.
EBI3, FOXP3, multiple sclerosis, RORC, T cells, transcription factors
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-64758DOI: 10.1177/1352458510381256ISI: 000285867200006PubMedID: 20847001OAI: oai:DiVA.org:liu-64758DiVA: diva2:394857