Secondary progressive in contrast to relapsing‐remitting multiple sclerosis patients show a normal CD4⁺CD25⁺ regulatory T‐cell function and FOXP3 expression

Abstract

Accumulating evidence indicates an immunosuppressive role for CD4(+)CD25(+) regulatory T cells (Tregs) in autoimmune diseases. Although an impaired Treg function in patients with relapsing-remitting multiple sclerosis (RR-MS) has been reported recently, no information is available so far about Treg function in the progressive stage of the disease. In the present study, the phenotypic and functional characteristics of CD4(+)CD25(+) T cells isolated from the peripheral blood of patients with RR-MS and secondary progressive multiple sclerosis (SP-MS) were investigated. No significant quantitative or phenotypic abnormalities in CD4(+)CD25(+) T cells from RR- and SP-MS patients were detected. However, whereas a reduced suppressor function of CD4(+)CD25(+) T cells toward proliferation and interferon-gamma production of CD4(+)CD25(-) responder T cells was found in RR-MS patients, SP-MS patients showed a normal Treg function. The suppressive capacity of MS-derived CD4(+)CD25(+) T cells was correlated with disease duration but not with age, indicating that Treg function is more affected in the early phase of the disease process. Consistently with the suppressive capacity, CD4(+)CD25(+) T cells from SP-MS patients showed normal levels of FOXP3 mRNA in contrast to RR-MS patients that had a reduced FOXP3 expression. These data are the first to demonstrate differences in function and FOXP3 expression of CD4(+)CD25(+) T cells from patients with RR- and SP-MS.

Involvement of T-cell receptor-β alterations in the development of otosclerosis linked to OTSC2

“…For various human autoimmune diseases, it was shown that peripheral Treg and NKT cell function or frequencies are disturbed. 32 In contrast, in OTSC2 patients we did not detect significant differences in the prevalence of these regulatory T cells. In addition, no differences were detected in activated T cells (CD3 þ CD25 int ).…”

HLA-DRB1*15 allele influences the later course of relapsing remitting multiple sclerosis

“…The number of patients in each group is shown in Table 2. In the total group, the median time to reach EDSS 6.0 was higher for DR15-negative as compared with DR15-positive patients: 25 [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] (Figure 2a), but the difference was not statistically significant. After stratification on MS form at onset, there was no significant difference in the median time to reach EDSS 6.0 between DR15-positive and DR15-negative patients (Figure 2b) in the PP group.…”

“…If we consider that HLA DR15 influences the conversion of RR to SP MS, we may speculate that HLA is not only implicated in the early phase of the disease (susceptibility) but also in the later course of MS. 25 …”

“…It was 20 years [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] in the total group, 31 years [26][27][28][29][30][31][32] in the RR MS group, 14 years [10][11][12][13][14][15][16][17][18][19][20] in the SP MS group and 9 years [6][7][8][9][10][11][12][13][14][15][16][17] in the PP MS group ( Figure 1). As expected, these figures were significantly Figure 1 Median time to reach Expanded Disease Status Scale (EDSS) 6 for all patients and patients stratified according to MS type.…”

Multiple Sclerosis and Regulatory T Cells

“…Vandenbark and coworkers, however, showed decreases in FoxP3 levels in Tregs isolated from patients with MS, and found that this decrease correlated with Treg loss of function [65]. Additionally, Venken et al, reported that relapsingremitting (but not secondary progressive) MS patients express lower levels of FoxP3 than healthy controls [66]. It is not yet clear from these studies whether lower FoxP3 expression in MS patients is due to a reduced frequency of FoxP3 + cells in the CD4 + CD25 hi T cell population or due to decreased FoxP3 expression at a cellular level.…”