title: Unravelling the complexity of T cell abnormalities in common variable immunodeficiency.
abstract: We investigated several phenotypic and functional parameters of T cell-mediated immunity in a large series of common variable immunodeficiency (CVID) patients. We demonstrated that the vast majority of CVID patients presented multiple T cell abnormalities intimately related among them, the severity of which was reflected in a parallel loss of CD4+ naive T cells. A strong correlation between the number of CD4+ naive T cells and clinical features was observed, supporting the subgrouping of patients according to their number of naive CD4+ T lymphocytes. A reduced thymic output and disrupted CD4+ and CD8+ TCR repertoires paralleled the contraction of CD4+ naive T cell pools. The evaluation of activation markers and cytokine production indicated a strong T cell activation that was significantly related to the increased levels of T cell turnover and apoptosis. Finally, discrete genetic profiles could be demonstrated in groups of patients showing extremely diverse T cell subset composition and function. Naive CD4+ T cell levels were significantly associated with the switched memory B cell-based classification, although the concordance between the respective subgroups did not exceed 58.8%. In conclusion, our data highlight the key role played by the T cell compartment in the pathogenesis of CVID, pointing to the need to consider this aspect for classification of this disease.
authors.affiliation: Department of Clinical Medicine, Division of Allergy and Clinical Immunology, La Sapienza University, Viale dell'Università 37, 00185 Rome, Italy. antonello.giovannetti@uniroma1.it
authors.forename: Antonello
authors.initials: A
authors.lastname: Giovannetti
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.forename: Francesca
authors.initials: F
authors.lastname: Mazzetta
authors.forename: Marco
authors.initials: M
authors.lastname: Marziali
authors.forename: Cristina
authors.initials: C
authors.lastname: Renzi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mileo
authors.forename: Marco
authors.initials: M
authors.lastname: De Felice
authors.forename: Barbara
authors.initials: B
authors.lastname: Mora
authors.forename: Antonella
authors.initials: A
authors.lastname: Esposito
authors.forename: Rossella
authors.initials: R
authors.lastname: Carello
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Marco G
authors.initials: MG
authors.lastname: Paggi
authors.forename: Roberto
authors.initials: R
authors.lastname: Paganelli
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.forename: Fernando
authors.initials: F
authors.lastname: Aiuti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D017074:Common Variable Immunodeficiency / Q000145:classification / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology