Unravelling the complexity of T cell abnormalities in common variable immunodeficiency |
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Authors: | Giovannetti Antonello Pierdominici Marina Mazzetta Francesca Marziali Marco Renzi Cristina Mileo Anna Maria De Felice Marco Mora Barbara Esposito Antonella Carello Rossella Pizzuti Antonio Paggi Marco G Paganelli Roberto Malorni Walter Aiuti Fernando |
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Institution: | Department of Clinical Medicine, Division of Allergy and Clinical Immunology, La Sapienza University, Viale dell'Università 37, 00185 Rome, Italy. antonello.giovannetti@uniroma1.it |
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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. |
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