Ken,
Regarding your question as to why responses to viruses in the skin don't
evoke anti-skin autoimmunity:
It is true, and Polly acknowledges, that a lytic viral infection of
keratinocytes may indeed release skin-specific antigens which are then
captured by Langerhans' cells that have also received a specific danger
signal. These cells will travel back to the lymph node where they will
act as immunogenic antigen presenting cells to elicit an immune response
against skin-specific antigens. Consider, however, what happens
subsequently. Activated effector anti-skin T cells will go out into the
skin, kill some uninfected skin cells, and then rest down to become
memory anti-skin T cells. It is true that the CTL-mediated destruction
of skin cells may be a source of more antigen to be picked up by
macrophages, but since the skin cells are now dying an apoptotic cell
death the macrophages do not upregulate costimulatory signals. In fact,
it is possible that cells dying by apoptosis may release substances
(?interleukin 1-B?) that specifically tell phagocytic cells NOT to
activate T cells. Eventually, the memory anti-skin T cells would
circulate out to the skin, see the skin-specific antigens presented by
the keratinocytes themselves, and become tolerized. This last idea is
Polly's; although an attractive hypothesis, I am not absolutely sure that
the only cell types that can reactivate memory T cells are professional
APCs and B cells.
Ephraim Fuchs
ejf at welchlink.welch.jhu.edu
