The T-cell pool is anergized in patients with multiple sclerosis in remission
Article first published online: 8 JUL 2008
© 2008 Blackwell Publishing Ltd
Volume 126, Issue 1, pages 92–101, January 2009
How to Cite
Fransson, M. E., Liljenfeldt, L. S. E., Fagius, J., Tötterman, T. H. and Loskog, A. S. I. (2009), The T-cell pool is anergized in patients with multiple sclerosis in remission. Immunology, 126: 92–101. doi: 10.1111/j.1365-2567.2008.02881.x
- Issue published online: 8 DEC 2008
- Article first published online: 8 JUL 2008
- Received 7 March 2008; revised 22 April 2008; accepted 13 May 2008.
- multiple sclerosis;
- T regulatory cells;
- T helper typ 1 1;
- T helper type 17
Relapsing–remitting multiple sclerosis (RRMS) is a complex autoimmune disease of the central nervous system with oscillating phases of relapse and remission. RRMS has been considered to be driven by T helper type 1 (Th1) lymphocytes but new data indicate the involvement of Th17 responses. In the present study, blood samples from patients (n = 48) and healthy individuals (n = 44) were evaluated for their immunological status. T cells from patients with RRMS expressed high levels of the activation marker CD28 (P < 0·05) and secreted both interferon-γ (CD8: P < 0·05) and interleukin-17 upon polyclonal mitogen or myelin oligodendrocyte glycoprotein antigen stimulation. However, T cells from patients with RRMS in remission, in contrast to relapse, had poor proliferative capacity (P < 0·05) suggesting that they are controlled and kept in anergy. This anergy could be broken with CD28 stimulation that restored the T-cell replication. Furthermore, the patients with RRMS had normal levels of CD4+ Foxp3+ T regulatory cells but the frequency of Foxp3+ cells lacking CD127 (interleukin-7 receptor) was lower in patients with MS (mean 12%) compared to healthy controls (mean 29%). Still, regulatory cells (CD25+ sorted cells) from patients with RRMS displayed no difference in suppressive capacity. In conclusion, patients in relapse/remission demonstrate in vitro T-cell responses that are both Th1 and Th17 that, while in remission, appear to be controlled by tolerogenic mechanisms yet to be investigated.