The TH1 phenotype of follicular helper T cells indicates an IFN-γ-associated immune dysregulation in patients with CD21low common variable immunodeficiency.
J Allergy Clin Immunol
; 141(2): 730-740, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-28554560
ABSTRACT
BACKGROUND:
A subgroup of patients with common variable immunodeficiency (CVID) experience immune dysregulation manifesting as autoimmunity, lymphoproliferation, and organ inflammation and thereby increasing morbidity and mortality. Therefore treatment of these complications demands a deeper comprehension of their cause and pathophysiology.OBJECTIVES:
On the basis of the identification of an interferon signature in patients with CVID with secondary complications and a skewed follicular helper T-cell differentiation in defined monogenic immunodeficiencies, we sought to determine the profile of CD4 memory T cells in blood and secondary lymphatic tissues of these patients.METHODS:
We quantified TH1/TH2/TH17 CD4 memory T cells in blood and lymph nodes of patients with CVID using flow cytometry, analyzed their function, and correlated all findings to the burden of immune dysregulation.RESULTS:
Patients with CVID with immune dysregulation had a skewed memory CD4 T-cell differentiation toward a CXCR3+CCR6- TH1 phenotype both in blood and lymph nodes. Consistent with our phenotypic findings, we observed a higher IFN-γ production in peripheral CD4 memory T cells and lymph node-derived follicular helper T cells of patients with CVID compared with those of healthy control subjects. Increased IFN-γ production was accompanied by a poor germinal center output, an accumulation of T-box transcription factor (T-bet)+ B cells in lymph nodes, and an accumulation of T-bet+CD21low B cells in peripheral blood of affected patients.CONCLUSION:
Identification of excessive IFN-γ production by blood and lymph node-derived T cells of patients with CVID with immune dysregulation will offer new therapeutic avenues for this subgroup. CD21low B cells might serve as a marker of this IFN-γ-associated dysregulation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon gama
/
Receptores de Complemento 3d
/
Imunodeficiência de Variável Comum
/
Células Th1
/
Memória Imunológica
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article