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Journal of Virology, September 1998, p. 7440-7449, Vol. 72, No. 9
Division of Virology,
Received 22 April 1998/Accepted 17 June 1998
CD8+ cytotoxic T lymphocytes (CTL) play a key role in
the control of many virus infections, and the need for vaccines to
elicit strong CD8+ T-cell responses in order to provide
optimal protection in such infections is increasingly apparent.
However, the mechanisms involved in the induction and maintenance of
CD8+ CTL memory are currently poorly understood. In this
study, we investigated the involvement of CD40 ligand (CD40L)-mediated
interactions in these processes by analyzing the memory CTL response of
CD40L-deficient mice following infection with lymphocytic
choriomeningitis virus (LCMV). The maintenance of memory
CD8+ CTL precursors (CTLp) at stable frequencies over time
was not impaired in CD40L-deficient mice. By contrast, the initial
generation of memory CTLp was affected. CD40L-deficient mice produced
lower levels of CD8+ CTLp during the primary immune
response to LCMV than did wild-type controls, despite the fact that the
LCMV-specific effector CTL response of CD40L-deficient mice was
indistinguishable from that of control animals. The differentiation of
naïve CD8+ T cells into effector and memory CTL
thus involves pathways that can be discriminated from each other by
their requirement for CD40L-mediated interactions. Expression of CD40L
by CTLp themselves was not an essential step during their expansion and
differentiation from naïve CD8+ cells into memory
CTLp; instead, the reduction in memory CTLp generation in
CD40L-deficient mice was likely a consequence of defects in the
CD4+ T-cell response mounted by these animals. These
results thus suggest a previously unappreciated role for CD40L in the
generation of CD8+ memory CTLp, the probable nature of
which is discussed.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
CD40 Ligand-Mediated Interactions Are Involved in
the Generation of Memory CD8+ Cytotoxic T Lymphocytes
(CTL) but Are Not Required for the Maintenance of CTL Memory
following Virus Infection
*
Corresponding author. Present address: The Edward
Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom. Phone: 1635 577913. Fax: 1635 577901. E-mail: seph.borrow{at}bbsrc.ac.uk.
Journal of Virology, September 1998, p. 7440-7449, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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