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 (BALB/c-tolerant)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.
Metcalfe
Su M
SM
Department of Surgery, University of Cambridge, Box 202, Level E9, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. smm1001@cam.ac.uk
Watson
Tracy J
TJ
Shurey
Sandra
S
Adams
Elizabeth
E
Green
Colin J
CJ
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D011506:Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators