Unravelling the complexity of T cell abnormalities in common variable immunodeficiency

Antonello Giovannetti, Marina Pierdominici, Francesca Mazzetta, Marco Marziali, Cristina Renzi, Anna Maria Mileo, Marco De Felice, Barbara Mora, Antonella Esposito, Rossella Carello, Antonio Pizzuti, Marco G. Paggi, Roberto Paganelli, Walter Malorni, Fernando Aiuti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3932-3943
Number of pages12
JournalJournal of Immunology
Volume178
Issue number6
Publication statusPublished - Mar 15 2007

ASJC Scopus subject areas

  • Immunology

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