TRANSPLANTATION IMMUNOLOGY - IS THE THERA PEUTIC MANIPULATION OF THE CYTOKINE NETWORK APPROPRIATE

Classical allograft rejection is a cellular-mediated immune response i n which the activation of the CD4(+) T helper (Th) cell plays a crucia l role. After activation the Th cell produces a variety of cytokines w hich are essential for initiating allograft rejection. Th cells can be distinguished by their cytokine profile. Th1 cells produce IL-2 and I FN gamma, which are associated with rejection. Th2 cells are character ized by the production of IL-4 and IL-10, cytokines which are found in models when tolerance is induced. These findings are called the ''Th1 /Th2 paradigm'' and lead to the following hypothesis: Th1 cells are re sponsible for allograft rejection and manipulation of the cytokine net work towards a Th2 type cytokine pattern results in tolerance or delay ed rejection. This study attempts to answer the question whether the T h1/Th2 paradigm is a pure association or corresponds to a mechanism wh ich might be used therapeutically. Allograft rejection in the absence of the proinflammatory cytokines IL-2 and IFN gamma occurs almost unal tered. Moreover, supplying the anti-inflammatory cytokines IL-4 and IL -10 did not result in delayed rejection. Therefore, therapeutic manipu lation of the very complex cytokine network will most likely fail. Blo cking cytokine-independent T cell activation might be a better concept for induction of allograft tolerance.