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Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression

(2008) JOURNAL OF IMMUNOLOGY. 180(9). p.6411-6420
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Abstract
Patients with relapsing-remitting multiple sclerosis (RR-MS) show a suboptimal CD4(+)CD25(+) regulatory T cell (Treg) function, whereas no Treg alterations are observed in secondary progressive MS (SP-MS) patients. To clarify the difference in Treg activity between early and chronic disease stages in MS, we analyzed the functional capacity and homeostatic parameters of naive CD4(+)CD25(+)CD127(low)CD45RA(+) Tregs (nTregs) and their memory counterparts CD4(+)CD25(+)CD127(low) CD45RO(+) Tregs (mTregs) in untreated MS patients and healthy controls. Interestingly, whereas the suppressive capacity of FACS-sorted nTregs was impaired in both early and chronic MS patients, only the latter group showed a restored mTreg function. Consistent with this observation, chronic MS patients had increased numbers of mTregs as compared with age-matched early MS patients, whereas nTreg frequencies did not differ significantly. TCR excision circle numbers were reduced in nTregs of early MS patients, suggestive of a diminished nTreg thymic output. Moreover, a decreased number of CD31(+) mTregs were observed in early vs chronic MS patients, indicating that inflammatory processes drive the homeostatic turnover of mTregs during the early disease stage. Additionally, early MS patients showed a more restricted nTreg and mTreg TCR BV gene profile as compared with healthy controls and chronic MS patients. Finally, analysis of IFN-beta and glatiramer acetate-treated MS patients showed that these immunomodulatory drugs modify nTreg homeostasis. Taken together, this study provides strong evidence for a disturbed thymic nTreg development and function in MS patients. Moreover, memory Treg but not naive Treg homeostasis recovers during disease progression.
Keywords
AUTOIMMUNE-DISEASE, TRANSCRIPTION FACTOR FOXP3, SUPPRESSIVE FUNCTION, PERIPHERAL-BLOOD, EXPRESSION, GUIDELINES, TOLERANCE, INDUCTION, FREQUENCY, RESPONSES

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Citation

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Chicago
Venken, Koen, Niels Hellings, Tom Broekmans, Karen Hensen, Jean-Luc Rummens, and Piet Stinissen. 2008. “Natural Naive CD4+CD25+CD127low Regulatory T Cell (Treg) Development and Function Are Disturbed in Multiple Sclerosis Patients: Recovery of Memory Treg Homeostasis During Disease Progression.” Journal of Immunology 180 (9): 6411–6420.
APA
Venken, K., Hellings, N., Broekmans, T., Hensen, K., Rummens, J.-L., & Stinissen, P. (2008). Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. JOURNAL OF IMMUNOLOGY, 180(9), 6411–6420.
Vancouver
1.
Venken K, Hellings N, Broekmans T, Hensen K, Rummens J-L, Stinissen P. Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. JOURNAL OF IMMUNOLOGY. 2008;180(9):6411–20.
MLA
Venken, Koen, Niels Hellings, Tom Broekmans, et al. “Natural Naive CD4+CD25+CD127low Regulatory T Cell (Treg) Development and Function Are Disturbed in Multiple Sclerosis Patients: Recovery of Memory Treg Homeostasis During Disease Progression.” JOURNAL OF IMMUNOLOGY 180.9 (2008): 6411–6420. Print.
@article{2071084,
  abstract     = {Patients with relapsing-remitting multiple sclerosis (RR-MS) show a suboptimal CD4(+)CD25(+) regulatory T cell (Treg) function, whereas no Treg alterations are observed in secondary progressive MS (SP-MS) patients. To clarify the difference in Treg activity between early and chronic disease stages in MS, we analyzed the functional capacity and homeostatic parameters of naive CD4(+)CD25(+)CD127(low)CD45RA(+) Tregs (nTregs) and their memory counterparts CD4(+)CD25(+)CD127(low) CD45RO(+) Tregs (mTregs) in untreated MS patients and healthy controls. Interestingly, whereas the suppressive capacity of FACS-sorted nTregs was impaired in both early and chronic MS patients, only the latter group showed a restored mTreg function. Consistent with this observation, chronic MS patients had increased numbers of mTregs as compared with age-matched early MS patients, whereas nTreg frequencies did not differ significantly. TCR excision circle numbers were reduced in nTregs of early MS patients, suggestive of a diminished nTreg thymic output. Moreover, a decreased number of CD31(+) mTregs were observed in early vs chronic MS patients, indicating that inflammatory processes drive the homeostatic turnover of mTregs during the early disease stage. Additionally, early MS patients showed a more restricted nTreg and mTreg TCR BV gene profile as compared with healthy controls and chronic MS patients. Finally, analysis of IFN-beta and glatiramer acetate-treated MS patients showed that these immunomodulatory drugs modify nTreg homeostasis. Taken together, this study provides strong evidence for a disturbed thymic nTreg development and function in MS patients. Moreover, memory Treg but not naive Treg homeostasis recovers during disease progression.},
  author       = {Venken, Koen and Hellings, Niels and Broekmans, Tom and Hensen, Karen and Rummens, Jean-Luc and Stinissen, Piet},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keywords     = {AUTOIMMUNE-DISEASE,TRANSCRIPTION FACTOR FOXP3,SUPPRESSIVE FUNCTION,PERIPHERAL-BLOOD,EXPRESSION,GUIDELINES,TOLERANCE,INDUCTION,FREQUENCY,RESPONSES},
  language     = {eng},
  number       = {9},
  pages        = {6411--6420},
  title        = {Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression},
  url          = {http://www.jimmunol.org/content/180/9/6411.abstract},
  volume       = {180},
  year         = {2008},
}

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