Leukemia inhibitory factor is linked to regulatory transplantation tolerance

Background. The specific regulation of allo-tolerance in vivo occurs within a complex microenvironment and involves co-operation between a small proportion of different cell types within the spleen or draining lymph node. By analyzing unmanipulated whole spleen cell populations we have aimed to mimic this in vivo situation to identify critical signaling molecules in regulatory allo-tolerance. Methods. We compared the kinetics of cytokine release and induction of signaling proteins in CBA, versus (BALB/c-rejected) CBA, spleen cells after challenge with BALB/c antigen. Results. The distinguishing features of allo-tolerance were Foxp3 protein expression, LIF release, and increased levels of STAT3. Comparison of isogenic clones of Tr1, Th1, and Th2 cells revealed that only the regulatory Tr1 cells are characterized by both LIF and IL10 release. Conclusions. Overall, our findings demonstrate that allo-antigen driven signaling events can be detected within a whole spleen cell population and identify a role for LIF in the regulation of transplantation tolerance in vivo.