Reproductive immunology 2003: reassessing the Th1/Th2 paradigm?

We briefly review the history of concepts (some of which are still valid) which have lead to the present situation where pregnancy is viewed as being a Th2 phenomenon. We recall some of the early evidence which has been taken as supporting the general validity of this concept in murine and human pregnancy. We then recall some of the recent data dealing with "newer" cytokines and the role of uterine natural killer (NK) cells at the feto-maternal interface which fit neither with a steady-state concept nor with inflammatory cytokines, being solely "bad guys" as the paradigm would predict, nor with the concept of reduction of NK "activity" being required for successful pregnancy. As an example of the newer complexity, we briefly recall some of our recent micro-array studies in mice, and describe briefly our most recent data in human pointing out the importance of the tripod IL-12/IL-18/NK in successful or failed pregnancy in human, perhaps under IL-15 control. We conclude by a repeated warning against the so-called rationales of lymphocyte alloimmunization for therapy of recurrent spontaneous abortion and improvement of implantation rates.