Inducible co-stimulatory molecules participate in mesenteric vascular endothelial-mesenchymal transition and sclerosis of mesenteric vessels in spontaneously hypertensive rats / 南方医科大学学报

OBJECTIVE@#To investigate the correlation of inducible co-stimulatory molecules (ICOS) with mesenteric vascular endothelial- mesenchymal transition (EndMT) and sclerosis in spontaneously hypertensive rats (SHR).@*METHODS@#Twenty 4-week-old WKY rats and 20 SHRs of the same strain were both randomly divided into 4 groups for observation at 4, 6, 10 and 30 weeks of age. ICOS expression frequency in rat spleen CD4+T cells was analyzed using flow cytometry, and the expressions of ICOS, VE-cad, α-SMA and Col3 mRNA in rat mesentery were detected by RT-PCR. The distributions of ICOS, IL-17A and TGF-β in rat mesentery were detected by immunohistochemistry. The levels of IL-17A and TGF-β in rat plasma were measured using ELISA. The morphological changes of rat mesenteric vessels were observed with Masson staining. Spearman or Pearson correlation analyses were used to evaluate the correlation between ICOS expression and the expressions of the markers of vascular EndMT and sclerosis.@*RESULTS@#Compared with the control WKY rats, the SHRs began to show significantly increased systolic blood pressure and ICOS expression frequency on CD4+T cells at 6 weeks of age (P < 0.05). In the SHRs, the mRNA and protein expressions of ICOS, α-SMA, Col3, IL-17A and TGF-β in the mesentery were significantly higher than those in control group (P < 0.05), while the mRNA and protein expressions of VE-cad started to reduce significantly at 10 weeks of age (P < 0.05). The plasma levels of IL-17A and TGF-β were significantly increased in SHRs since 6 weeks of age (P < 0.05) with progressive worsening of mesenteric vascular sclerosis (P < 0.05). ICOS mRNA and protein expression levels in the mesenteric tissues of SHRs began to show positive correlations with α-SMA and Col3 expression levels and the severity of vascular sclerosis at 6 weeks of age (P < 0.05) and a negative correlation with VE-cad expression level at 10 weeks (P < 0.05).@*CONCLUSION@#ICOS play an important pathogenic role in EndMT and sclerosis of mesenteric vessels in essential hypertension by mediating related immune responses.

Fluorescent tracer technique using ICOS-Ab marked with Cy7. SE for diagnosing acute heart graft rejection in mice / 第二军医大学学报

Objective To establish a non-invasive method based on fluorescent tracer technique using inducible co-stimulatory molecules(ICOS) expressed on activated T cells for diagnosing acute heart graft rejection in mice. Methods The cervical heterotopic heart transplantation was used as model to establish isograft, allograft, allograft plus tacrolimus treatment, and allograft with tacrolimus ceased groups. On the 1, 3rd, 5th and 7th day after transplantation, Cy7. SE-ICOS-Ab was injected into the heart transplant mice via tail veins. The real-time fluorescent imaging changes of the graft were observed by fluorescent equipment. Flow cytometry was used to examine the expression of ICOS on spleen T cells of mice in each group. H-E staining was used to observe the pathological changes of cardiac graft. Results There was no noticeable fluorescent imaging in the grafts at the 1, 3rd, 5th and 7th day after transplantation in the isograft and allograft with tacrolimus treatment group. On the first day after transplantation, the fluorescent imaging of graft in the allograft group had no noticeable changes, but the fluorescent imaging gradually increased on the 3rd, 5th, and 7th day. The graft fluorescent imaging became stronger on the 3rd day after ceasing tacrolimus in the treated allograft group, and it became stronger at 5 and 7 days after ceasing tacrolimus. H-E staining found no noticeable rejection in isograft group and allograft plus tacrolimus treatment group at all time points. The allograft and allograft puls tacrolimus ceased group developed rejection on the 3rd day after transplantation, and the rejection became more serious on the 5th and 7th day. Flow cytometry showed that there were no significant differences in ICOS expression on spleen T cells on the 1 day after transplantation among the four groups (P>0. 05). The isograft and allograft plus tacrolimus treatment group had no ICOS expression on the T cells, and ICOS expression in the allograft and allograft with tacrolimus ceased group gradually increased on the 3rd, 5th and 7th day. Conclusion ICOS expression intensity is associated with the degree of graft rejection. Fluorescently labeled anti-ICOS can help to assess the development and severity of acute rejection after transplantation in a non-invasive way.

Expression of Inducible Co-stimulator in Peripheral Blood T Lymphocytes in the Patients with Systemic Lupus Erythematosus / 华中科技大学学报（医学）（英德文版）

Summary: The expression of inducible co-stimulator (ICOS) in peripheral blood T lymphocytes from the patients with systemic lupus erythematosus (SLE) and the role in the pathogenesis of SLE was investigated. By using two-color immunofluorescent staining and flow cytometric assay, the expression levels of ICOS in peripheal blood T lymphocytes from 33 patients with SLE and 16 healthy volunteers were detected. SLE diseases activity index (SLEDAI) of the patients with SLE was used to evaluate the disease activity. The correlation between the ICOS expression and SLEDAI was analyzed among the groups. The results showed that the expression levels of ICOS in T lymphocytes in active SLE group was markedly higher than those in the control and inactive SLE groups (both P<0.01). There was no significant difference in the expression levels of ICOS between the inactive SLE and the control groups (P>0.05). In active SLE and inactive SLE groups, positive linear correlation was found between the levels of the ICOS expression in T lymphocytes and SLEDAI (r=0.711, P＝0.001; r=0.561, P＝0.03). It was suggested that the expression of ICOS in peripheral blood T lymphocytes from the patients with active SLE was up-regulated and and ICOS might be related to the pathogenesis of SLE.

Expression of Inducible Co-Stimulator on T lymphocytes in Peripheral Blood from the Patients with Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To investigate the expression of inducible co-stimulator (ICOS) on T lymphocytes in peripheral blood from the patients with systemic lupus erythematosus (SLE). Methods Two-color immunofluorescent staining and flow cytometric assay were used to analyze the level of ICOS expression on T lymphocytes in peripheral blood from 33 SLE patients and 16 healthy volunteers. The data of systemic lupus erythematosus diseases activity index (SLEDAI) in SLE patients were also collected. Results The level of ICOS expression on T cells from active SLE group was markedly higher than that in the control group and the inactive SLE group (P 0.05). However, a positive correlation between the expression level of ICOS and the SLEDAI score was found in both active SLE group and inactive SLE group(r = 0.711,P = 0.001?r = 0.561,P = 0.03). Conclusions The expression of ICOS on T cell in peripheral blood from active SLE is increased, which might play a role in the pathogenesis of SLE.