Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report

被引：21

作者：

Cicalese, Maria Pia ^{[1
,2
,3
]}

Gerosa, Jolanda ^{[4
]}

Baronio, Manuela ^{[5
,6
]}

Montin, Davide ^{[7
]}

Licciardi, Francesco ^{[7
]}

Soresina, Annarosa ^{[8
]}

Dellepiane, Rosa Maria ^{[9
]}

Miano, Maurizio ^{[10
]}

Baselli, Lucia Augusta ^{[9
]}

Volpi, Stefano ^{[11
]}

Dufour, Carlo ^{[10
,11
]}

Plebani, Alessandro ^{[5
,6
]}

Aiuti, Alessandro ^{[1
,2
,3
]}

Lougaris, Vassilios ^{[5
]}

Fousteri, Georgia ^{[4
]}

机构：

[1] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy HSR TIGET, IRCCS, Milan, Italy

[2] Ist Sci San Raffaele, Pediat Immunohematol & Bone Marrow Transplantat U, IRCCS, Milan, Italy

[3] Univ Vita Salute San Raffaele, Milan, Italy

[4] Ist Sci San Raffaele, IRCCS, Diabet Res Inst, DITID, Milan, Italy

[5] Univ Brescia, Dept Clin & Expt Sci, Pediat Clin, ASST Spedali Civili Brescia, Brescia, Italy

[6] Univ Brescia, Inst Mol Med A Novicelli, ASST Spedali Civili Brescia, Brescia, Italy

[7] Citta Salute & Sci Torino, Regina Margherita Hosp, Dept Paediat 2, Immunorheumatol, Turin, Italy

[8] ASST Spedali Civili Brescia, Pediat Clin, Brescia, Italy

[9] Univ Milan, Dept Pediat, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

[10] IRCCS Inst Giannina Gaslini, Dept Ematooncol, Genoa, Italy

[11] IRCCS Inst Giannina Gaslini, Dept Pediat, Genoa, Italy

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

关键词：

hyper-IgM syndrome; follicular helper T cells; follicular regulatory T cells; class switch recombination; somatic hypermutation; AICDA; CD40LG; CD40; HYPER-IGM SYNDROME; INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; GERMINAL CENTER FORMATION; AUTOSOMAL RECESSIVE FORM; B-CELLS; ACTIVATION; TOLERANCE; AID; EXPRESSION;

D O I：

10.3389/fimmu.2018.01761

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Mutations in genes that control class switch recombination and somatic hypermutation during the germinal center (GC) response can cause diverse immune dysfunctions. In particular, mutations in CD40LG, CD40, AICDA, or UNG cause hyper-IgM (HIGM) syndrome, a heterogeneous group of primary immunodeficiencies. Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play a key role in the formation and regulation of GCs, but their role in HIGM pathogenesis is still limited. Here, we found that compared to CD40 ligand (CD40L)-and activation-induced cytidine deaminase (AICDA)-deficient patients, circulating Tfh and Tfr cells were severely compromised in terms of frequency and activation phenotype in a child with CD40 deficiency. These findings offer useful insight for human Tfh biology, with potential implications for understanding the molecular basis of HIGM syndrome caused by mutations in CD40.

引用

页数：8

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