The Cd4(+) Cd25(+) Regulatory T Cell Profile and Foxp3 Expression and Clinic Associations of in Various Stage and Types of Multiple Sclerosis

Yıl 2018, Cilt: 40 Sayı: 1, 7 - 13, 27.02.2018

Mustafa Men Demet İlhan Algın Ceyhan Kutlu Zafer Gülbaş

https://doi.org/10.20515/otd.320243

Cited By: 1

Öz

In
the pathogenesis of MS, impairment of peripheric immune tolerance plays an
important critical role in the emergence of autoimmunity. The regulatory T
cells play a crucial role in the healthy function of immune tolerance. FoxP3 is
a transcription factor which assignment for enough regulatory T cell
expression.  We compared the total
percentage CD4(+) and FoxP3 expression in T lymphocytes in 31 cases including
12 RRMS, 11 SRMS and eight attack which has a definite MS regarding Mc Donald's
criteria 12 healthy subjects for regulatory T cell subtypes with analysis flow
cytometry in haematology laboratory. Also, we compared 7 cases in a group of 8
RRMS with an attack for before and after 1000 mg/day IVMP.  The results have assesment as statistical.
The regulatory cell profiles CD4(+) CD25(+), CD4(+) foxP3(+), CD4(+) CD25(+)
foxP3(+),CD4(+) CD25(+) foxP3(-), and CD4(+) CD25(-) foxP3(+)of all patients
were compared with the healthy control group.No significant differences existed
between the groups (p>0.005). The results of regulatory cell profiles and
foxP3 expression of 7 patients with attacks before treatment and after IVMP
treatment were not significant (p>0.05). However, high-dose intravenous
methylprednisolone therapy (IVMP) treatment was observed to cause a slight
numerical increase in regulatory cell subtypes. As a consequence, we thought
that the regulatory T cells play an important role in the immunopathogenesis of
MS as well as its numerical sufficiency. 

Anahtar Kelimeler

MS, immune tolerance, foxP3

Multipl Skleroz’un Değişik Klinik Tiplerinde ve Farkli Evrelerinde Cd4(+) Cd25(+) Regülatuar T Hücre Profili ve Foxp3 Ekspresyonu

Öz

Multipl Skleroz
patogenezinde otoimmunitenin ortaya çıkışında periferik immun toleransın
bozulması önemli rol oynamaktadır. İmmun toleransın sağlıklı işleyişinde
regülatuvar T hücreleri ise anahtar rol oynamaktadır. FoxP3 ise regülatuvar T
hücreler yeterli ekpresyonu için transkripsiyon faktörü olarak görev
almaktadır. Biz bu çalışmayla Mc Donald’s 
kriterlerine göre klinik olarak kesin MS tanısı almış 12 RRMS (relapsing
Remitting Multipl skleroz), 11 SRMS ( Sekonder Relapsing Multipl skleroz), 8
atak RRMS hastası olmak üzere toplam 31 hasta ile 12 sağlıklı kontrol gurubunun
regülatuvar T hücre alt tipleri hematoloji laboratuarında akım sitometrisi ile
analiz ederek total CD4(+) T lenfosit içerisindeki yüzdeleri ve FoxP3
ekspresyonunu karşılaştırdık. Ataklı 8 RRMS hastasının ise 7 tanesi 1000 mg/
gün İVMP tedavisinden önce ve tedaviden sonra kendi içinde karşılaştırıldı.
Sonuçlar istatiksel olarak değerlendirildi. Regülatuvar T hücre profili  CD4(+) CD25(+), CD4(+) foxP3(+), CD4(+)
CD25(+) foxP3(+),CD4(+) CD25(+) foxP3(-), ve CD4(+) CD25(-) foxP3(+)
karşılaştırıldı, hastalar ve kontrol grubu arasında anlamlı fark bulunmadı
(p>0.005). Atak öncesi ve atak sonrası IVMP tedavisi sonrası 7 hastanın
regülatör hücre profilleri  ve foxP3
ekspresyonu arasında anlamlı fark saptanmadı (p>0.05). Ancak, yüksek doz
intravenöz metilprednizolon (IVMP) tedavisinin 
regülatör  hücre alt tipleri  içinde hafif bir sayısal artış neden olduğu
gözlenmiştir. Regülatuvar T hücrelerin MS imunopatogenezinde sayısal
yeterliliği yanında işlevsel özelliklerinin önemli rol oynadığı düşünüldü.

Anahtar Kelimeler

MS, foxP3, immun toleransı, regülatuvar hücre

Kaynakça

• REFERENCES 1- Weiner LH. Multiple sclerosis is an inflammatory T-Cell-mediated autoimmune diease. Archives Neurology. 2004;61(10):1613-1615.
• 2- Piccirillo AC, Shevach ME. Naturally occuring CD4(+)CD25(+) immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin İmmunol. 2004;16(2):81-88.
• 3- Imitola J, Chitnis T, Khoury SJ. Insights into the molecular pathogenesis of progression in multiple sclerosis. Archives Neurology. 2006;63(1):25-33.
• 4- O’Connor KC, Bar-or A, Hafler DA. The Neuroimmunology of Multiple Sclerosis: Possible Roles ofT and B Lymphocytes in Immunopathogenesis. Journal of Clinical Immunology. 2001;21(2):81-92.
• 5- Hong J, Zang YC, Nie H, Zhang JZ. CD4+ regulatory T cell responses induced by T cell vaccination in patients with multiple sclerosis. Proc Natl acad Sci USA. 2006;28;103(13):5024-5029.
• 6- Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs developmentand function of CD4(+)CD25(+) regulatory T cells. Nature immunology. 2003;4(4):330-335.
• 7- McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-7.
• 8- Huan J, Culbertson N, Spencer L, Bartholomew R, Burrows GG, Chou YK, et al. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res. 2005;81(1):45-52.
• 9- Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of Functional Suppression by CD4(+) CD25(+) Regulatory T Cells in Patients with Multiple Sclerosis. J. Exp. Med. 2004;199(7):971–979.
• 10- Valencia X, Lipsky PE. CD4+ CD25+ FoxP3+ regulatory Tcells in autoimmune diseases. Nat Clin Pract Rheumatol .2007;3(11):619-626.
• 11- Seddon B, Mason D. Peripheral autoantigen induces regulatory T cells that prevent autoimmunity. J Exp Med. 1999;189(5):877–882.
• 12- Herrmann MM, Gaertner S, Stadelmann C, van den Brandt J, Böscke R, Budach W, et al. Tolerance induction by bone marrow transplantation in a multiple sclerosis model. Blood. 2005;106(5):1875-1883.
• 13- Serra P, Amrani A, Yamanouchi J, Han B, Thiessen S, Utsugi T, et al. CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells. Immunity. 2003;19(6):877–889.
• 14- Nie J, Li YY, Zheng SG, Tsun A, Li B. FOXP3(+) Treg Cells and Gender Bias İn Autoimmune Diseases. Front Immunol. 2015;28;6(1):493.
• 15- Sarween N, Chodos A , Raykundalia C, Khan M, Abbas AK, Walker LS. CD4(+) CD25(+)Cells Controlling a Pathogenic CD4(+) Response Inhibit Cytokine Differentiation, CXCR-3 Expression. The Journal of Immunology. 2004;173(5): 2942–2951.
• 16- Venken K, Hellings N, Hensen K, Rummens JL, Meader R, D’hooghe, et al. Secondary progressive in contrast to relapsingremitting multiple sclerosis patients show a normal CD4+CD25+ regulatory T-cell function and FOXP3 expression. J Neurosci Res. 2006;83(8):1432-446.
• 17- Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens JL, et al. Compromised CD4+ CD25(high) 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 singlecell level. Immunology. 2008;123(1):79-89.
• 18- Jensena J, Langkild AR, Fenst C, Nicolaisen MS, Roed HG, Christiansen M,et al. CD4 T cell activation and disease activity at onset of multiple sclerosis. Journal of Neuroimmunology. 2004;149(1-2):202–209.
• 19- Ohashi T. Short-term high-dose intravenous methylprednisolone therapy. Nihon Rinsho. 2014;72(11):1995-8.
• 20- Noori-Zadeh A, Mesbah-Namin SA, Bistoon-Beigloo S, Bakhtiyari S, Abbaszadeh HA, Darabi S, et al. Regulatory T cell number in multiple sclerosis patients:A meta-analysis.Mult Scler Relat Disord. 2016;5;73-6.
• 21- Wanga HY, Matsuia M, Araya S, Onai N, Matsushima K, Saida T. Immune parameters associated with early treatment effects of highdoseintravenous methylprednisolone in multiple sclerosis. Journal of the Neurological Sciences. 2003;216(1):61-66.
• 22- Navarro J, Aristimuño C, Sánchez-Ramón S, Vigil D, Martinez-Gines ML, Fernandez-Ceruz E, de Andres C. Circulating dendritic cells subsets and regulatory T-cells at multiple sclerosis relapse: Differential short-term changes on corticosteroids therapy. J Neuroimmunol. 2006;176(1-2);153-161.