Decreased Frequencies of Circulating Follicular Helper T Cell Counterparts and Plasmablasts in Ankylosing Spondylitis Patients Naive for TNF Blockers

被引：34

作者：

Bautista-Caro, Maria-Belen ^{[1
]}

Arroyo-Villa, Irene ^{[1
]}

Castillo-Gallego, Concepcion ^{[1
]}

de Miguel, Eugenio ^{[1
]}

Peiteado, Diana ^{[1
]}

Plasencia-Rodriguez, Chamaida ^{[1
]}

Villalba, Alejandro ^{[1
]}

Sanchez-Mateos, Paloma ^{[2
]}

Puig-Kroeger, Amaya ^{[2
]}

Martin-Mola, Emilio ^{[1
]}

Miranda-Carus, Maria-Eugenia ^{[1
]}

机构：

[1] Hosp Univ La Paz IdiPAZ, Dept Rheumatol, Madrid, Spain

[2] Hosp Gen Univ Gregorio Maranon, Lab Inmunooncol, Madrid, Spain

来源：

PLOS ONE | 2014年 / 9卷 / 09期

关键词：

SOCIETY CLASSIFICATION CRITERIA; CXC CHEMOKINE RECEPTOR-5; SYSTEMIC AUTOIMMUNITY; AXIAL SPONDYLOARTHRITIS; DISEASE-ACTIVITY; RESPONSES; IMMUNITY; GUT; INFLAMMATION; PERMEABILITY;

D O I：

10.1371/journal.pone.0107086

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Follicular helper T cells (Tfh), localized in lymphoid organs, promote B cell differentiation and function. Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of Tfh. Three subpopulations of circulating CD4+CXCR5+ cells have been described: CXCR3+CCR6-(Tfh-Th1), CXCR3-CCR6+ (Tfh-Th17), and CXCR3-CCR6-(Tfh-Th2). Only Tfh-Th17 and Tfh-Th2 function as B cell helpers. Our objective was to study the frequencies of circulating Tfh (cTfh), cTfh subsets and plasmablasts (CD19+CD20-CD27+CD38(high) cells), and the function of cTfh cells, in patients with Ankylosing Spondylitis (AS). To this end, peripheral blood was drawn from healthy controls (HC) (n = 50), AS patients naive for TNF blockers (AS/nb) (n = 25) and AS patients treated with TNF blockers (AS/b) (n = 25). The frequencies of cTfh and plasmablasts were determined by flow cytometry. Cocultures of magnetically sorted CD4+CXCR5+ T cells with autologous CD19+ CD27-naive B cells were established from 3 AS/nb patients and 3 HC, and concentrations of IgG, A and M were measured in supernatants. We obseved that AS/nb but not AS/b patients, demonstrated decreased frequencies of circulating CD4+CXCR5+ICOS+PD-1+ cells and plasmablasts, together with a decreased (Tfh-Th17+ Tfh-Th2)/Tfh-Th1 ratio. The amounts of IgG and IgA produced in cocultures of CD4+CXCR5+ T cells with CD19+CD27-B cells of AS/nb patients were significantly lower than observed in cocultures established from HC. In summary, AS/nb but not AS/b patients, demonstrate a decreased frequency of cTfh and plasmablasts, and an underrepresentation of cTfh subsets bearing a B helper phenotype. In addition, peripheral blood CD4+CXCR5+ T cells of AS/nb patients showed a decreased capacity to help B cells ex vivo.

引用

页数：11

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