Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report
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 immunodeficie...
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doaj-d31e6288c914441486635ff1670779a92020-11-24T20:49:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01761356944Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case ReportMaria Pia Cicalese0Maria Pia Cicalese1Maria Pia Cicalese2Jolanda Gerosa3Manuela Baronio4Davide Montin5Francesco Licciardi6Annarosa Soresina7Rosa Maria Dellepiane8Maurizio Miano9Lucia Augusta Baselli10Stefano Volpi11Carlo Dufour12Carlo Dufour13Alessandro Plebani14Alessandro Aiuti15Alessandro Aiuti16Alessandro Aiuti17Vassilios Lougaris18Georgia Fousteri19San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, ItalyPediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyDivision of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI) IRCCS San Raffaele Scientific Institute, Milan, ItalyDepartment of Clinical and Experimental Sciences, Pediatrics Clinic and Institute of Molecular Medicine A. Novicelli, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, ItalyImmuno-Rheumatology, Department of Paediatrics II, Regina Margherita Hospital, Città della Salute e della Scienza di Torino, Torino, ItalyImmuno-Rheumatology, Department of Paediatrics II, Regina Margherita Hospital, Città della Salute e della Scienza di Torino, Torino, ItalyPediatrics Clinic, ASST-Spedali Civili di Brescia, Brescia, ItalyDepartment of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, ItalyDepartment of Emato-Oncology, IRCCS Instituto Giannina Gaslini, Genoa, ItalyDepartment of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy0Department of Pediatrics, IRCCS Instituto Giannina Gaslini, Genoa, ItalyDepartment of Emato-Oncology, IRCCS Instituto Giannina Gaslini, Genoa, Italy0Department of Pediatrics, IRCCS Instituto Giannina Gaslini, Genoa, ItalyDepartment of Clinical and Experimental Sciences, Pediatrics Clinic and Institute of Molecular Medicine A. Novicelli, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, ItalySan Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, ItalyPediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyDepartment of Clinical and Experimental Sciences, Pediatrics Clinic and Institute of Molecular Medicine A. Novicelli, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, ItalyDivision of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI) IRCCS San Raffaele Scientific Institute, Milan, ItalyMutations 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.01761/fullhyper-IgM syndromefollicular helper T cellsfollicular regulatory T cellsclass switch recombinationsomatic hypermutationAICDA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Pia Cicalese Maria Pia Cicalese Maria Pia Cicalese Jolanda Gerosa Manuela Baronio Davide Montin Francesco Licciardi Annarosa Soresina Rosa Maria Dellepiane Maurizio Miano Lucia Augusta Baselli Stefano Volpi Carlo Dufour Carlo Dufour Alessandro Plebani Alessandro Aiuti Alessandro Aiuti Alessandro Aiuti Vassilios Lougaris Georgia Fousteri |
spellingShingle |
Maria Pia Cicalese Maria Pia Cicalese Maria Pia Cicalese Jolanda Gerosa Manuela Baronio Davide Montin Francesco Licciardi Annarosa Soresina Rosa Maria Dellepiane Maurizio Miano Lucia Augusta Baselli Stefano Volpi Carlo Dufour Carlo Dufour Alessandro Plebani Alessandro Aiuti Alessandro Aiuti Alessandro Aiuti Vassilios Lougaris Georgia Fousteri Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report Frontiers in Immunology hyper-IgM syndrome follicular helper T cells follicular regulatory T cells class switch recombination somatic hypermutation AICDA |
author_facet |
Maria Pia Cicalese Maria Pia Cicalese Maria Pia Cicalese Jolanda Gerosa Manuela Baronio Davide Montin Francesco Licciardi Annarosa Soresina Rosa Maria Dellepiane Maurizio Miano Lucia Augusta Baselli Stefano Volpi Carlo Dufour Carlo Dufour Alessandro Plebani Alessandro Aiuti Alessandro Aiuti Alessandro Aiuti Vassilios Lougaris Georgia Fousteri |
author_sort |
Maria Pia Cicalese |
title |
Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report |
title_short |
Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report |
title_full |
Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report |
title_fullStr |
Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report |
title_full_unstemmed |
Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report |
title_sort |
circulating follicular helper and follicular regulatory t cells are severely compromised in human cd40 deficiency: a case report |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-08-01 |
description |
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. |
topic |
hyper-IgM syndrome follicular helper T cells follicular regulatory T cells class switch recombination somatic hypermutation AICDA |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01761/full |
work_keys_str_mv |
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