Abstract Book 2010 - CIMT Annual Meeting

025 Savelyeva | Immune monitoring
Vaccination and immune memory: modelling the bystander
activation of CD4+ memory T cells in mice
Natalia Savelyeva, Amy Suchacki, Stephen Thirdborough, Freda K. Stevenson & Gianfranco Di Genova
Cancer Sciences Division, Southampton University Hospitals, Tremona RD, Southampton, UK
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CD4+ T-helper (Th) cells have a key role in pro-
moting both B and T cell-mediated immunity.
Knowledge of the mechanisms involved in the
maintenance of vaccine-induced or natural CD4
T cell immunity is crucial for the development of
successful vaccination strategies against infectious
diseases and cancer. We previously demonstrated
that in healthy volunteers vaccination with tetanus
toxoid (TT) induced bystander activation of Th
memory cells of unrelated specificities; however
antibody responses by B cells remained vaccinespecific
(Di Genova G et al. Blood 2006). We hypothesized
that this bystander activation could
represent a mechanism which contributes to their
long-term maintenance. We have now modelled
this phenomenon in mice, confirming the results
observed in humans and paving the way to a better
understanding of the immunological mechanisms
responsible for it. Briefly, in a first model two populations
of CD4+ memory T cells specific for two
distinct antigens were generated simultaneously in
C57BL/6 mice. When mice were re-challenged with
one of the two antigens, this caused not only the
expected recall immune response but also expansion
in the number of cytokine-producing cells specific
for the unrelated antigen. In a second model,
CD4+ TCR transgenic T cells (OT-II), either naïve or
previously activated in vitro with cognate antigen,
were CFSE-labelled and transferred into wild type
recipient mice which were immune to TT. Recipient
mice were then challenged with TT antigen and
susceptibility of OT-II cells to bystander activation
and proliferation was tested. Antigen-activated but
not naïve cells were responsive and underwent bystander
proliferation. This was proportional to the
strength of the TT-specific memory T-cell response
and appeared to be mediated by the common
gamma chain cytokines IL-2 and IL-7. These data
support the principle that CD4+ T cells at various
stages of differentiation, from activated to memory
cells, can respond to cytokines generated during
parallel immune responses, such as those induced
in human subjects by vaccines or natural exposure
to environmental antigens. This might represent a
mechanism which could contribute to their antigenindependent
maintenance. The findings have high
relevance for the measurement of T-cell responses
in patients who are being vaccinated.