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