Intragraft overexpression of interleukin-4 is neither sufficient nor essential for tolerance induction to cardiac allografts in a high-responder strain combination.

Background. Recently we have demonstrated that the nondepleting anti-CD4 mo noclonal antibody (mAb) RIB5/2 induces long-term acceptance of kidney and h eart allografts in all rat strain combinations tested. Cytokine gene expres sion studies by reverse transcriptase-polymerase chain reaction revealed a reversed intragraft interleukin (IL)-4/interferon-gamma ratio. Whether IL-4 mediated immune deviation contributes to transplantation tolerance is not clear so far. Methods. To learn more about the functional relevance of the relative IL-4 up-regulation, IL-4 was overexpressed in rat heart allografts by using ex v ivo adenoviral gene transfer. The efficiency of gene transfer was analyzed by reporter gene assays as well by reverse transcriptase-polymerase chain r eaction analysis of IL-4 mRNA expression. Results. The intragraft overexpression of IL-4 did not prolong the allograf t survival compared with controls. Moreover, neutralization of IL-4 by OX81 mAb did not pl event tolerance induction by RIB5/2 treatment, Conclusions. Anti-CD4 mAb-induced tolerance is associated with an intragraf t type1/type2 shift, however, the up-regulation of IL-4 alone is neither su fficient nor essential to induce tolerance to cardiac allografts in a high- responder strain combination.