The Expression Of BTLA, Cbl-b MRNA In Experimental Allergic Neuritis

Objective Guillain-Barr(?) syndrome(GBS) is regard as a kind of autoimmune peripheral neuropathies.Now the exact pathogenesis and mechanism of GBS remains poorly understood.Experimental allergic neuritis(EAN) is a CD4⁺ T cell mediated animal model of GBS, characterized by inflammation and demyelination of the peripheral nervous system(PNS).Many studies confirm the breakdown of immunotolerance and induction of autoreactive T cell is an important mechanism for both GBS and EAN.B and T lymphocyte attenuator (BTLA),an inhibitory receptor on T lymphocytes,can decrease the proliferation of T cells and attenuates production of interleukin-2 after crossing with ligand.E3 ubiquitin ligase Casitas B-lineage lymphoma b(Cbl-b),as a negative regulator of T-cell activation,is an intrinsic mediator of T cell anergy that maintain the balance between tolerance, activation,and autoimmunity.In this study,we investigated the levels of BTLA and Cbl-b mRNA in EAN rats.To study the involvement of BTLA and Cbl-b in EAN will give us new target for treating autoimmune disease.Methods 72 male Lewis rats were divided into 3 randomized groups, called NS group,CFA group,and EAN group.Rats were immunized by injection into both bind footpads with altogether 200μl emulsion containing 100μg P₂53-78aa peptid emulsified in 100μl PBS and 100μl complete Freund's adjuvant.Observe the clinical signs of rats and pathological changes in the sciatic nerves.The rats in immunized and control group were sacrificed on the 7day,16day,24day,and 33day post immunization(p.i).Embed sciatic to make paraffin section and stain it by HE stain and Weil's stain to observe the histopathology.Using reverse transcriptase polymerase chain reaction(RT-PCR),we thus investigated the levels of BTLA and Cbl-b mRNA in spleens,sciatic nerves, peripheral blood lymphocytes and lymphonodes.Result:EAN group got the peak of clinical score on the 16d p.i,and the clinical manifestation ameliorated obviously on the 33d p.i.The level of BTLA mRNA was upregulated during the whole process of the experiment,and was higher compared with the control group,P＜0.05.The mRNA expression of Cbl-b was weakened during the whole process of the experiment,got the lowest peak on the 16d.p.i,and there was significance difference compared with the neighbor point(P＜0.05). During the convalescence,Cbl-b increased gradually,but it was still lower that the CFA control group on the 33d.p.i(P＜0.05).CFA group and NS group didn't show any clinical manifestation.Compared with NS group,the mRNA expression of BTLA and Cbl-b mRNA in CFA group was no difference(P＞0.05).The mRNA expression of BTLA and Cbl-b in each tissue correlates with each other.Conclusion:The dynamic expression of BTLA and Cbl-b mRNA indicates they may play a role in the pathogenesis of EAN.