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Compromised CD4+ CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level

(2008) IMMUNOLOGY. 123(1). p.79-89
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Abstract
CD4(+) CD25(high) regulatory T cells (Tregs) of patients with relapsing-remitting (RR) multiple sclerosis (MS), in contrast to those of patients with secondary progressive (SP) MS, show a reduced suppressive function. In this study, we analysed forkhead box P3 (FOXP3) at the single-cell level in MS patients and controls (healthy individuals and patients with other neurological diseases) by means of intracellular flow cytometry. Our data revealed a reduced number of peripheral blood CD4(+) CD25(high) FOXP3(+) T cells and lower FOXP3 protein expression per cell in RR-MS patients than in SP-MS patients and control individuals, which was correlated with the suppressive capacity of Tregs in these patients. Interestingly, interferon (IFN)-beta-treated RR-MS patients showed restored numbers of FOXP3(+) Tregs. Furthermore, a higher percentage of CD4(+) CD25(high) FOXP3(+) Tregs in RR-MS patients, as compared with controls and SP-MS patients, expressed CD103 and CD49d, adhesion molecules involved in T-cell recruitment towards inflamed tissues. This was consistent with a significantly increased number of CD27(+) CD25(high) CD4(+) T cells in the cerebrospinal fluid (CSF), as compared with peripheral blood, in RR-MS patients. Taken together, these data show aberrant FOXP3 expression at the single-cell level correlated with Treg dysfunction in RR-MS patients. Our results also suggest that Tregs accumulate in the CSF of RR-MS patients, in an attempt to down-regulate local inflammation in the central nervous system.
Keywords
DENDRITIC CELLS, IMMUNE-RESPONSE, REVISED CRITERIA, AUTOIMMUNE-DISEASE, RHEUMATOID-ARTHRITIS, multiple sclerosis, tolerance, regulatory T cells, FOXP3, SYSTEMIC-LUPUS-ERYTHEMATOSUS, TRANSCRIPTION FACTOR FOXP3, CENTRAL-NERVOUS-SYSTEM, NAIVE CD4, L-SELECTIN, autoimmunity

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Citation

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MLA
Venken, Koen, Niels Hellings, Marielle Thewissen, et al. “Compromised CD4+ CD25high Regulatory T-cell Function in Patients with Relapsing-remitting Multiple Sclerosis Is Correlated with a Reduced Frequency of FOXP3-positive Cells and Reduced FOXP3 Expression at the Single-cell Level.” IMMUNOLOGY 123.1 (2008): 79–89. Print.
APA
Venken, K., Hellings, N., Thewissen, M., Somers, V., Hensen, K., Rummens, J.-L., Medaer, R., et al. (2008). Compromised CD4+ CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. IMMUNOLOGY, 123(1), 79–89.
Chicago author-date
Venken, Koen, Niels Hellings, Marielle Thewissen, Veerle Somers, Karen Hensen, Jean-Luc Rummens, Robert Medaer, Raymond Hupperts, and Piet Stinissen. 2008. “Compromised CD4+ CD25high Regulatory T-cell Function in Patients with Relapsing-remitting Multiple Sclerosis Is Correlated with a Reduced Frequency of FOXP3-positive Cells and Reduced FOXP3 Expression at the Single-cell Level.” Immunology 123 (1): 79–89.
Chicago author-date (all authors)
Venken, Koen, Niels Hellings, Marielle Thewissen, Veerle Somers, Karen Hensen, Jean-Luc Rummens, Robert Medaer, Raymond Hupperts, and Piet Stinissen. 2008. “Compromised CD4+ CD25high Regulatory T-cell Function in Patients with Relapsing-remitting Multiple Sclerosis Is Correlated with a Reduced Frequency of FOXP3-positive Cells and Reduced FOXP3 Expression at the Single-cell Level.” Immunology 123 (1): 79–89.
Vancouver
1.
Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens J-L, et al. Compromised CD4+ CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. IMMUNOLOGY. 2008;123(1):79–89.
IEEE
[1]
K. Venken et al., “Compromised CD4+ CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level,” IMMUNOLOGY, vol. 123, no. 1, pp. 79–89, 2008.
@article{2071091,
  abstract     = {CD4(+) CD25(high) regulatory T cells (Tregs) of patients with relapsing-remitting (RR) multiple sclerosis (MS), in contrast to those of patients with secondary progressive (SP) MS, show a reduced suppressive function. In this study, we analysed forkhead box P3 (FOXP3) at the single-cell level in MS patients and controls (healthy individuals and patients with other neurological diseases) by means of intracellular flow cytometry. Our data revealed a reduced number of peripheral blood CD4(+) CD25(high) FOXP3(+) T cells and lower FOXP3 protein expression per cell in RR-MS patients than in SP-MS patients and control individuals, which was correlated with the suppressive capacity of Tregs in these patients. Interestingly, interferon (IFN)-beta-treated RR-MS patients showed restored numbers of FOXP3(+) Tregs. Furthermore, a higher percentage of CD4(+) CD25(high) FOXP3(+) Tregs in RR-MS patients, as compared with controls and SP-MS patients, expressed CD103 and CD49d, adhesion molecules involved in T-cell recruitment towards inflamed tissues. This was consistent with a significantly increased number of CD27(+) CD25(high) CD4(+) T cells in the cerebrospinal fluid (CSF), as compared with peripheral blood, in RR-MS patients. Taken together, these data show aberrant FOXP3 expression at the single-cell level correlated with Treg dysfunction in RR-MS patients. Our results also suggest that Tregs accumulate in the CSF of RR-MS patients, in an attempt to down-regulate local inflammation in the central nervous system.},
  author       = {Venken, Koen and Hellings, Niels and Thewissen, Marielle and Somers, Veerle and Hensen, Karen and Rummens, Jean-Luc and Medaer, Robert and Hupperts, Raymond and Stinissen, Piet},
  issn         = {0019-2805},
  journal      = {IMMUNOLOGY},
  keywords     = {DENDRITIC CELLS,IMMUNE-RESPONSE,REVISED CRITERIA,AUTOIMMUNE-DISEASE,RHEUMATOID-ARTHRITIS,multiple sclerosis,tolerance,regulatory T cells,FOXP3,SYSTEMIC-LUPUS-ERYTHEMATOSUS,TRANSCRIPTION FACTOR FOXP3,CENTRAL-NERVOUS-SYSTEM,NAIVE CD4,L-SELECTIN,autoimmunity},
  language     = {eng},
  number       = {1},
  pages        = {79--89},
  title        = {Compromised CD4+ CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level},
  url          = {http://dx.doi.org/10.1111/j.1365-2567.2007.02690.x},
  volume       = {123},
  year         = {2008},
}

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