Interleukin-21: an interleukin-2 dependent player in rejection processes.
Transplantation
; 83(11): 1485-92, 2007 Jun 15.
Article
in En
| MEDLINE
| ID: mdl-17565322
ABSTRACT
BACKGROUND:
Interleukin (IL)-21 is the most recently described cytokine that signals via the common cytokine receptor (gammac), is produced by activated CD4+ T-cells, and regulates expansion and effector function of CD8+ T-cells. MATERIALS To explore the actions of IL-21 with other gammac-dependent cytokines in alloreactivity, mRNA expression of IL-21, IL-21R alpha-chain, and IL-2 proliferation and cytotoxicity was measured after stimulation in mixed lymphocyte reactions. Additionally, IL-21 and IL-21R alpha-chain expression was studied in biopsies of heart transplant patients.RESULTS:
Analysis of mRNA expression levels of allostimulated T-cells showed a 10-fold induction of IL-21 and IL-21R alpha-chain. Interestingly, induction of IL-21 was highly dependent on IL-2 (as in the presence of anti-IL-2, anti-IL-2R alpha-chain, and the immunosuppressive drugs cyclosporine A, tacrolimus, and rapamycin) the transcription of IL-21 was almost completely inhibited, whereas in the presence of exogenous IL-2 the mRNA expression of IL-21 was even more upregulated. IL-21 functioned as a costimulator for IL-2 to augment proliferation and cytotoxic responses, while blockade of the IL-2 route abrogated these functions of IL-21. Blockade of the IL-21 route by anti-IL-21R alpha-chain monoclonal antibodies inhibited the proliferation of alloactivated T-cells. Also, in vivo alloreactivity was associated with IL-21/IL-21R alpha-chain expression. After heart transplantation, the highest intragraft IL-21, IL-21R alpha-chain, and IL-2 mRNA expression levels were measured during acute rejection (P<0.001, P=0.01, P=0.03).CONCLUSION:
IL-21 is a critical cytokine for IL-2 dependent immune processes. Blockade of the IL-21 pathway may provide a new perspective for the treatment of allogeneic responses in patients after transplantation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Heart Transplantation
/
Interleukins
/
Interleukin-2
/
Graft Rejection
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Transplantation
Year:
2007
Document type:
Article
Affiliation country: