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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2131-2137
IMMUNOBIOLOGY
Long-lasting memory-resting and memory-effector CD4+
T cells in human X-linked agammaglobulinemia
Marino Paroli,
Daniele Accapezzato,
Vittorio Francavilla,
Antonella Insalaco,
Alessandro Plebani,
Francesco Balsano, and
Vincenzo Barnaba
From the Fondazione Andrea Cesalpino, Dipartimento di
Medicina Interna, Università di Roma La Sapienza, Rome, Italy;
Dipartimento di Pediatria and Istituto di Medicina Molecolare Angelo
Nocivelli, Università di Brescia, Italy; and Istituto
Pasteur-Cenci Bolognetti, Rome, Italy.
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 (TH2)
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- ,
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 TH1/TH2 balance.
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