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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.


Left column: Net % changes of regulatory/effector ratios (CD4+CD25+/CD4+CD25−) after 72 h culture of PBMC of MS patients and HC with the antigenic peptides PEP1-4 or cP7; Right column: Net % changes in the corresponding anti-inflammatory/inflammatory cytokine ratios ([IL-4 + IL-10]/[IFN-γ + TNF-α + IL-17A]) in the culture supernatants.
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ijms-17-01398-f005: Left column: Net % changes of regulatory/effector ratios (CD4+CD25+/CD4+CD25−) after 72 h culture of PBMC of MS patients and HC with the antigenic peptides PEP1-4 or cP7; Right column: Net % changes in the corresponding anti-inflammatory/inflammatory cytokine ratios ([IL-4 + IL-10]/[IFN-γ + TNF-α + IL-17A]) in the culture supernatants.

Mentions: To delineate the effects of disease state and treatment regimens on nTreg responses, the numbers of CD4+CD25− and CD4+CD25+ cells were measured in cultures ± peptides, to calculate the ratio of effector to suppressor cells, as well as the percentage of CD4+CD25+Foxp3+ nTregs. The net change of effector/suppressor ratios between cultures ± peptides was also calculated, to assess any shift towards an effector or suppressor phenotype. Positive changes reflected an effector shift whereas negative a suppressor shift (Figure 5, left column). These changes were accompanied by corresponding changes in cytokine ratios, with an increase in anti-inflammatory cytokines when a suppressor shift was observed (Figure 5, right column).


Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens
Left column: Net % changes of regulatory/effector ratios (CD4+CD25+/CD4+CD25−) after 72 h culture of PBMC of MS patients and HC with the antigenic peptides PEP1-4 or cP7; Right column: Net % changes in the corresponding anti-inflammatory/inflammatory cytokine ratios ([IL-4 + IL-10]/[IFN-γ + TNF-α + IL-17A]) in the culture supernatants.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-17-01398-f005: Left column: Net % changes of regulatory/effector ratios (CD4+CD25+/CD4+CD25−) after 72 h culture of PBMC of MS patients and HC with the antigenic peptides PEP1-4 or cP7; Right column: Net % changes in the corresponding anti-inflammatory/inflammatory cytokine ratios ([IL-4 + IL-10]/[IFN-γ + TNF-α + IL-17A]) in the culture supernatants.
Mentions: To delineate the effects of disease state and treatment regimens on nTreg responses, the numbers of CD4+CD25− and CD4+CD25+ cells were measured in cultures ± peptides, to calculate the ratio of effector to suppressor cells, as well as the percentage of CD4+CD25+Foxp3+ nTregs. The net change of effector/suppressor ratios between cultures ± peptides was also calculated, to assess any shift towards an effector or suppressor phenotype. Positive changes reflected an effector shift whereas negative a suppressor shift (Figure 5, left column). These changes were accompanied by corresponding changes in cytokine ratios, with an increase in anti-inflammatory cytokines when a suppressor shift was observed (Figure 5, right column).

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.