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Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens

View Article: PubMed Central - PubMed

ABSTRACT

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4+CD25highFoxp3+ (nTregs), CD3+CD4+HLA−G+, CD3+CD8+CD28−, CD3+CD56+, and CD56bright cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3+CD4+HLA−G+ and CD3+CD8+CD28− RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3+CD56+, and patients in remission + natalizumab the highest levels of CD56bright cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction.

No MeSH data available.


Related in: MedlinePlus

(A) Effector/suppressor ratios of HC and patient groups after cultures of PBMC in the absence of antigenic peptides. Note the complementarity with the CD4+CD25highFoxp3+ frequencies in Figure 1. * p = 0.05; and (B) correlation of effector/suppressor ratios in culture, with the percentage of corresponding CD4+CD25highFoxp3+ Tregs (Spearman r = −0.64, p < 0.0001).
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ijms-17-01398-f006: (A) Effector/suppressor ratios of HC and patient groups after cultures of PBMC in the absence of antigenic peptides. Note the complementarity with the CD4+CD25highFoxp3+ frequencies in Figure 1. * p = 0.05; and (B) correlation of effector/suppressor ratios in culture, with the percentage of corresponding CD4+CD25highFoxp3+ Tregs (Spearman r = −0.64, p < 0.0001).

Mentions: Effector/suppressor ratios in cultures-peptides showed a reverse trend to that of nTregs in peripheral blood (Figure 6). The higher ratios were observed in AP-noRx, AP-MP, and Rem-NATA patients, and the lower in AP-IFN patients (Figure 6A). This observation was confirmed by a strong inverse correlation between effector/suppressor ratios and CD4+CD25+Foxp3+ T-cells (r = −0.64, p < 0.0001) (Figure 6B).


Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens
(A) Effector/suppressor ratios of HC and patient groups after cultures of PBMC in the absence of antigenic peptides. Note the complementarity with the CD4+CD25highFoxp3+ frequencies in Figure 1. * p = 0.05; and (B) correlation of effector/suppressor ratios in culture, with the percentage of corresponding CD4+CD25highFoxp3+ Tregs (Spearman r = −0.64, p < 0.0001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037678&req=5

ijms-17-01398-f006: (A) Effector/suppressor ratios of HC and patient groups after cultures of PBMC in the absence of antigenic peptides. Note the complementarity with the CD4+CD25highFoxp3+ frequencies in Figure 1. * p = 0.05; and (B) correlation of effector/suppressor ratios in culture, with the percentage of corresponding CD4+CD25highFoxp3+ Tregs (Spearman r = −0.64, p < 0.0001).
Mentions: Effector/suppressor ratios in cultures-peptides showed a reverse trend to that of nTregs in peripheral blood (Figure 6). The higher ratios were observed in AP-noRx, AP-MP, and Rem-NATA patients, and the lower in AP-IFN patients (Figure 6A). This observation was confirmed by a strong inverse correlation between effector/suppressor ratios and CD4+CD25+Foxp3+ T-cells (r = −0.64, p < 0.0001) (Figure 6B).

View Article: PubMed Central - PubMed

ABSTRACT

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4+CD25highFoxp3+ (nTregs), CD3+CD4+HLA&minus;G+, CD3+CD8+CD28&minus;, CD3+CD56+, and CD56bright cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase &plusmn; methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3+CD4+HLA&minus;G+ and CD3+CD8+CD28&minus; RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3+CD56+, and patients in remission + natalizumab the highest levels of CD56bright cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction.

No MeSH data available.


Related in: MedlinePlus