Yuchuan Huang

Do CD4+ Foxp3+ Treg cells correlate with transplant outcomes: a systematic review on recipients of solid organ transplantation.

Regulatory T cells (Tregs) are considered to be critical for the induction of transplant tolerance. Tregs counts were measured in blood, biopsy and urine sample after transplantation in many studies. Although not unanimous, some studies have suggested that Tregs is associated with better outcome and can also serve as an immune marker to predict the individual risk of rejection and identify tolerant patients. In this study, we systematically reviewed the correlation between Tregs and transplant outcomes, identifying if Tregs can predict transplant rejection and tolerance. A total of 22 articles were included and assessed, the results showed that Tregs in recipients are helpful to maintain a stable graft function, reduce acute/chronic rejection rate. And the Tregs in graft and urine, rather than in PBL, may have a better diagnostic value for transplant outcomes. However, since the low quality of included studies, results may be influenced by bias. More high quality studies with bigger sample size are still needed in future.

Rapamycin in combination with donor-specific CD4+CD25+Treg cells amplified in vitro might be realize the immune tolerance in clinical organ transplantation

It is an urgent need to induce and keep the donor-specific immune tolerance without affecting the function of normal immune defense and immune surveillance in clinical organ transplantation. Large number of studies showed that both the establishment of donor-recipient chimerism and the application of antibodies or drugs could obtain the donor-specific immune tolerance in animal transplantation model. However, the former as treatment of clinical practice has a poor feasibility, the latter has a very low success rate in clinical organ transplantation. There is a group of naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) that mediate immune tolerance by suppressing alloreactive T cells in vivo. These cells are unable to curb the occurrence of allograft rejection owing their low content. And donor-specific Tregs amplified in vitro alone can not induce donor-specific immune tolerance for recipient. Rapamycin (RPM) as a proliferation signal inhibitor, studies have shown it can effectively inhibit allograft rejection and maybe contribute to induction of immune tolerance. But there exist still many dose-dependent adverse reactions which could prevent the establishment of immune tolerance and reduce the life quality of recipients in the clinical application of RPM. Therefore, we speculate a small amount of RPM combined with donor-specific Tregs amplified in vitro may be not only induce the achievement of donor-specific tolerance, but also reduce or eliminate the side effects of RPM in clinical organ transplantation.

Peripheral blood T Regulatory cell counts may not predict transplant rejection

BackgroundRecent evidence shows that allograft survival rates show a positive correlation with the number of circulating T regulatory cells (Tregs). This study investigated both the number and the cytokine profiles exhibited by Foxp3+ Tregs in blood, spleen and lymph nodes of Lewis rat recipients of BN rat cardiac allografts after a single-dose of Rapamycin (RAPA).ResultsRats were divided into three groups: control group (containing healthy control and acute rejection group), and recipients treated with a single dose of RAPA on either Day 1 (1D group)or Day 3 (3D group) post-transplant. We analyzed the number of Foxp3+Tregs and the expression of Foxp3 and cytokines in the peripheral blood and the peripheral lymphoid tissues. No difference was found in the numbers of circulating Foxp3+ Tregs between these three groups. RAPA administration significantly increased Foxp3 expression in peripheral lymphoid tissues after a single dose of RAPA on Day 3 post-transplant. Foxp3+Tregs inhibited the activity of effector T cells (Teff) via the secretion of TGF-β1.ConclusionThe number of Tregs in the recipients blood may not be a good predictor of transplant rejection. Foxp3+Tregs inhibit the activity of Teff cells mainly in the peripheral lymphoid tissues.

Combination of rapamycin and IL-2 do not affect antigen presentation ability of rat B cell and could promote Tregs proliferation and inhibitory activity

Rapamycin (RPM), a powerful agent used clinically in transplant recipients, induces CD4(+)CD25(+) regulatory T cells (Tregs) which play an important role in induction of immune tolerance. However, long-term use of RPM has negative side effects. In this report, we found that combination with the low dose RPM and high dose IL-2 did not affect antigen presentation of rat B cells to Tregs, and could efficiently promote Tregs proliferation and enhance their inhibitory activities in vitro. In addition, the combination of low dose RPM and high dose IL-2 enhanced mRNA expression of Foxp3, TGF-beta1 and Pim-2 in Tregs but not in CD4(+)CD25(-) T effector cells (Teffs). The Tregs inhibitory activity is positively associated with mRNA expressions of TGF-beta1 and Pim-2 while unrelated to the Foxp3 mRNA expression. Our present study offers one approach to expand functional Tregs in vitro, which maybe used for clinical immune tolerance induction.

Donor-specific regulatory T cells might be used to induce tolerance in solid organ transplantation

tion for treatment of all kinds of end-stage diseases. The success of organ transplantation owes much to improvements in the immunosuppressive regimens which induce allograft tolerance. Nevertheless, because the potent immunosuppressive drugs that are now in general use can have adverse effects not directly related to immunosuppression, there is a dramatically need to select specific and relatively nontoxic immunosuppressive agents or achieve some state of immune tolerance by other mechanisms. Recent evidence shows T cellmediated immunoregulation is one of the main mechanisms that are responsible for keeping antigen-specific operational tolerance in vivo [1,2]. Naturally occurring CD4CD25 regulatory T cells (Tregs) represent 5–10% of CD4 T cells in mice and are also found in human blood [3,4]. Tregs can be generated either from thymus or periphery, and their function is to control immune responses to infections and transplants [5,6]. Recent reports have shown that Tregs proliferate and retain their antigen-dependent suppressive function in a dosedependence manner when the APCs are antigenloaded mature dendritic cells [7,8]. Tregs specific for certain presented alloantigens can prevent both acute and chronic allograft rejection to induce lifelong immunological tolerance [2].