%0 Journal Article
%T Reciprocal role of cyclins and cyclin kinase inhibitor p21WAF1/CIP1 on lymphocyte proliferation, allo-immune activation and inflammation
%A Ashwani K Khanna
%J BMC Immunology
%D 2005
%I BioMed Central
%R 10.1186/1471-2172-6-22
%X We performed in vitro and in vivo studies using lymphocytes, and rat heart transplant model to understand the role of cyclins and p21 on mitogen and allo-induced lymphocyte activation and inflammation. Lymphocyte proliferation was studied by 3H-thymidine uptake assay and mRNA expression was studied RT-PCR.Activation of allo- and mitogen stimulated lymphocytes resulted in increased expression of cyclins, IL-2 and pro-inflammatory cytokines, which was inhibited by cyclosporine. The over-expression of p21 prolonged graft survival in a completely mismatched rat heart transplant model resulted by inhibiting circulating and intra-graft expression of proinflammatory cytokines.Cyclins play a significant role in transplant-induced immune activation and p21 over-expression has potential to inhibit T cell activation and inflammation. The results from this study will permit the design of alternate strategies by controlling cell cycle progression to achieve immunosuppression in transplantation.Alloimmune activation, caused by aberrant T lymphocyte proliferation is one of the key post transplant events in organ transplant recipients. Current immunosuppressive drugs are therefore designed to inhibit T lymphocyte proliferation. Our previous studies have demonstrated that immunosuppressive drugs, cyclosporine (CsA) tacrolimus (TAC), and sirolimus (SRL) besides inhibiting lymphocyte proliferation and IL-2 also induce the expression of TGF-¦Â and other fibrogenic molecules [1-3] leading to nephrotoxicity and chronic rejection. Therefore, there is a need to develop alternate strategies to achieve immunosuppression for increased graft survival with least nephrotoxicity. The most effective immunosuppression can be achieved by the direct inhibition of T lymphocyte proliferation. Since the expression of cyclins and cyclin-dependent kinases and pro-inflammatory cytokines is increased during T lymphocyte proliferation (4), control of T cell proliferation by regulating the expression of cyclin
%U http://www.biomedcentral.com/1471-2172/6/22