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

Frontiers in Immunology

Stefano Volpi¹  Carlo Dufour¹  Vassilios Lougaris²  Alessandro Plebani²  Manuela Baronio²  Maurizio Miano³  Rosa Maria Dellepiane⁴  Lucia Augusta Baselli⁴  Jolanda Gerosa⁵  Georgia Fousteri⁵  Davide Montin⁶  Francesco Licciardi⁶  Annarosa Soresina⁸  Maria Pia Cicalese^1,10  Alessandro Aiuti^1,10 

[1] 0Department of Pediatrics, IRCCS Instituto Giannina Gaslini, Genoa, Italy;Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute of Molecular Medicine A. Novicelli, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy;Department of Emato-Oncology, IRCCS Instituto Giannina Gaslini, Genoa, Italy;Department of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI) IRCCS San Raffaele Scientific Institute, Milan, Italy;Immuno-Rheumatology, Department of Paediatrics II, Regina Margherita Hospital, Città della Salute e della Scienza di Torino, Torino, Italy;Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy;Pediatrics Clinic, ASST-Spedali Civili di Brescia, Brescia, Italy;San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy;Vita-Salute San Raffaele University, Milan, Italy;

关键词: hyper-IgM syndrome;    follicular helper T cells;    follicular regulatory T cells;    class switch recombination;    somatic hypermutation;    AICDA;   

DOI  :  10.3389/fimmu.2018.01761

来源: DOAJ

【 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.

【 授权许可】

Unknown