Polly Matzinger's theory

Mike Clark mrc7 at cam.ac.uk
Thu Jun 20 13:03:11 EST 1996

Related to the discussions taking place here concerning how a T-cell decides
whether to respond or not I wonder if I could drag in a recent paper which I
find quite interesting and would like to find out how others respond?

The paper is Larsen et al Nature Vol 381, 434-438 (1996) "Long-term
acceptance of skin and cardiac allografts after blocking CD40 and CD28

The data in this paper is most interesting in that it looks like they may be
able to induce complete non-responsiveness in T-cells to allografts by using
simultaneous blockade of B7-1 and B7-2 plus gp39 (CD40L). To me the data looks
very convincing but what also interests me is that the effect is abolished by 
including CyA in the treatment.

Now I would have liked to have seen the result of re-grafting those mice to
find out if the non-responsiveness is actually tolerance. If it is it
obviously gives a big clue as to the requirements for tolerence induction
to major antigen mismatches and hence the full range of signals that
the T-cell is responding to. It also points to a more important role
for CD40.

Oh and of course it's bad news for those who are trying to induce tolerance
in patients who are also being treated with CyA!

Mike Clark, mrc7 at cam.ac.uk          http://www.path.cam.ac.uk/~mrc7/
  o/ \\    //            ||  ,_ o   Dr. M.R. Clark, Division of Immunology
 <\__,\\  //   __o       || /  /\,  Cambridge University, Dept. Pathology
  ">    ||   _`\<,_    //  \\ \> |  Tennis Court Rd., Cambridge CB2 1QP
   `    ||  (_)/ (_)  //    \\ \_   Tel. 01223 333705  Fax. 01223 333875

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