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Infection and Immunity, July 2000, p. 4264-4273, Vol. 68, No. 7
INSERM U4471 and
CNRS UMR 8527,3 Institut de Biologie de
Lille, Institut Pasteur de Lille, Lille, and INSERM E9922,
Groupe Hospitalier Bichat-Claude Bernard,
Paris,2 France
Received 13 September 1999/Returned for modification 1 November
1999/Accepted 7 March 2000
It has previously been reported that inhibition of delayed-type
hypersensitivity-mediating functions of T cells during mycobacterial infection in mice is haplotype dependent. In the present study, we show
that Mycobacterium bovis BCG infection induced, in
susceptible C57BL/6 and BALB/c mice but not in resistant C3H/HeJ and
DBA/2 mice, an important splenomegaly. An in vitro defect in T-cell proliferation in response to T-cell receptor (TCR) stimulation with
mitogens or anti-CD3 antibodies was associated with enhanced levels of
CD4+ and CD8+ T-cell apoptosis in susceptible
but not in resistant mice 2 weeks after infection. Further
investigations of C57BL/6 and C3H/HeJ mice revealed that in vivo
splenomegaly was associated with destruction of the lymphoid tissue
architecture, liver cellular infiltrates, and increased numbers of
apoptotic cells in both spleen and liver tissue sections. Infection of
C57BL/6 mice but not of C3H/HeJ mice induced massive production of
tumor necrosis factor alpha (TNF-
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Ineffective Cellular Immune Response Associated
with T-Cell Apoptosis in Susceptible Mycobacterium bovis
BCG-Infected Mice

) in serum, as well as an increase
in Fas and Fas ligand (FasL) expression in T cells. In vitro addition
of neutralizing anti-TNF-
antibodies led to a significant reduction
in CD3-induced T-cell apoptosis of both CD4+ and
CD8+ T cells of C57BL/6 mice, while the blockade of
Fas-FasL interactions reduced apoptosis only in CD4+ but
not in CD8+ T cells. Together, these results suggest that
TNF-
and Fas-FasL interactions play a role in the activation-induced
cell death (AICD) process associated with a defect in T-cell
proliferation of the susceptible C57BL/6 mice. T-cell death by
apoptosis may represent one of the important components of the
ineffective immune response against mycobacterium-induced
immunopathology in susceptible hosts.
*
Corresponding author. Mailing address: INSERM E9922,
Groupe Hospitalier Bichat-Claude Bernard, 16 rue Henri Huchard, 75018 Paris, France. Phone: (33) 1 44 85 62 88. Fax: (33) 1 44 85 62 88. E-mail: estaquie{at}bichat.inserm.fr.
Present address: Department of Microbiology and Immunology, The
Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne
NE2 4HH, United Kingdom.
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