Long-lasting memory-resting and memory-effector CD4+ T cells in human X-linked agammaglobulinemia.
Conflicting results obtained from animal studies suggest that B cells play a role in maintaining long-term T-cell memory and in skewing T-cell response toward a T-helper 2 (T(H)2) phenotype. X-linked agammaglobulinemia (XLA) is a genetic human disease characterized by the lack of circulating B cells due to the mutation of Bruton tyrosine kinase. This disease thus represents a unique model for studying the role of B lymphocytes in regulating T-cell functions in humans. To this aim, we analyzed hepatitis B envelope antigen (HBenvAg)-specific T-cell memory in a series of XLA patients vaccinated against hepatitis B virus (HBV). We found HBenvAg-specific T lymphocytes producing interferon-gamma, interleukin-4, or both in the peripheral blood of XLA patients up to at least 24 months after completing the standard anti-HBV immunization protocol. The HBenvAg-specific T-cell frequencies and the percentage of patients with these responses were not significantly different from healthy vaccinated controls. By combining cell purification and enzyme-linked immunospot assay, we found that effector CD27- T cells, which promptly produced cytokines in response to antigen (Ag), and memory-resting CD27+ T cells, which required Ag restimulation to perform their functions, were maintained in both XLA patients and controls for up to 24 months after the last vaccination boost. These data strongly suggest that B cells are not an absolute requirement for the generation of effective T-cell memory in humans, nor do they seem to influence T(H)1/T(H)2 balance.
Paroli
Marino
M
Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna, Università di Roma La Sapienza, Policlinico Umberto I, Via le del Policlinico 155, 00161 Rome, Italy.
Accapezzato
Daniele
D
Francavilla
Vittorio
V
Insalaco
Antonella
A
Plebani
Alessandro
A
Balsano
Francesco
F
Barnaba
Vincenzo
V
D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D008040:Genetic Linkage; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014960:X Chromosome
D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4; D007371:Interferon-gamma