Transcriptional characteristics of CD4+ T cells in multiple sclerosis: Relative lack of suppressive populations in blood

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(+)CD25(hi) Treg. Immunoregulatory EBI3 and Th2-associated GATA3 expression 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.