A role for antigen in the maintenance of immunological memory
Abstract
The immune system has a memory that it
exhibits in the enhanced and augmented
responses the second time it meets an
antigen. The memory is the result of a
number of changes to the system brought
about during the primary response. The
most important of these changes is the
formation of an expanded pool of antigenspecific
memory cells. One of the
enduring questions in immunology is how
these memory cells are maintained for
such long periods.
Until about 10 years ago, memory cells were
thought to be very long-lived cells that
required little, if any, external input to keep
them alive. This view arose not out of data
showing long cellular lifespans, but from the
observation that memory responses could be
elicited many years after immunization or
infection. It has been a common failure in
thinking about immunological memory to
imbue the individual cells with properties of
the whole system. Around 10–12 years ago, a
number of studies were published that highlighted
the influence of antigen on the survival
of memory cells. These studies indicated
that although the antigen-specific clones were
long-lived, the constituent memory cells were
relatively short-lived and required continued
antigenic stimulation (1–3). In the intervening period, the argument about antigen dependence
has continued, and recent experiments
have swung opinion back towards an antigenindependent
view. In this article, I wish to
argue that in reality, as opposed to experimental
models, the role of antigen in memory
maintenance is a very important one, and that
antigen persistence might be a crucial asset
for any vaccine.