[Transplantation immunology: is the manipulation of the cytokine network therapeutically justified?]

Classical allograft rejection is a cellular-mediated immune response in which the activation of the CD4+ T helper (Th) cell plays a crucial role. After activation the Th cell produces a variety of cytokines which are essential for initiating allograft rejection. Th cells can be distinguished by their cytokine profile. Th 1 cells produce IL-2 and IFN gamma, which are associated with rejection. Th2 cells are characterized 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 responsible for allograft rejection and manipulation of the cytokine network towards a Th2 type cytokine pattern results in tolerance or delayed rejection. This study attempts to answer the question whether the Th1/Th2 paradigm is a pure association or corresponds to a mechanism which might be used therapeutically. Allograft rejection in the absence of the proinflammatory cytokines IL-2 and IFN gamma occurs almost unaltered. Moreover, supplying the anti-inflammatory cytokines IL-4 and IL-10 did not result in delayed rejection. Therefore, therapeutic manipulation of the very complex cytokine network will most likely fail. Blocking cytokine-independent T cell activation might be a better concept for induction of allograft tolerance.