CD4+CD25+ T regulatory cells in renal transplantation

Abstract

The immune response to an allograft activates lymphocytes with the capacity to cause rejection. Activation of CD4+CD25+Foxp3+T regulatory cells (Treg) can down-regulate allograft rejection and can induce immune tolerance to the allograft. Treg represent <10% of peripheral CD4+T cells and do not markedly increase in tolerant hosts. CD4+CD25+Foxp3+T cells include both resting and activated Treg that can be distinguished by several markers, many of which are also expressed by effector T cells. More detailed characterization of Treg to identify increased activated antigen-specific Treg may allow reduction of non-specific immunosuppression. Natural thymus derived resting Treg (tTreg) are CD4+CD25+Foxp3+T cells and only partially inhibit alloantigen presenting cell activation of effector cells. Cytokines produced by activated effector cells activate these tTreg to more potent alloantigen-activated Treg that may promote a state of operational tolerance. Activated Treg can be distinguished by several molecules they are induced to express, or whose expression they have suppressed. These include CD45RA/RO, cytokine receptors, chemokine receptors that alter pathways of migration and transcription factors, cytokines and suppression mediating molecules. As the total Treg population does not increase in operational tolerance, it is the activated Treg which may be the most informative to monitor. Here we review the methods used to monitor peripheral Treg, the effect of immunosuppressive regimens on Treg, and correlations with clinical outcomes such as graft survival and rejection. Experimental therapies involving ex vivo Treg expansion and administration in renal transplantation are not reviewed.

Preparation and application of fluorescent monoclonal antibodies recognizing goat CD4+CD25+ regulatory T cells

“…CD25 and CD4 are considered phenotypic markers on the surface of regulatory T cells (Cheung et al 2022 ; Ng et al 2001 ). In this study, our data demonstrate that in local lesion tissues, Treg cells are recruited to the site of inflammation in ORFV-infected goats (Fig.…”

FOXP3 full length splice variant is associated with kidney allograft tolerance

“…We developed several primer pairs to measure the FOXP3 mRNA variant that lacks exon 2 and 7 ( Supplementary Table 5 ). This FOXP3 splice variant accounts for less than 3% of FOXP3 transcripts in human T regulatory cells ( 9 ), and its expression may even be lower in kidney transplant recipients because immunosuppressive therapy may decrease T regulatory cell abundance and FOXP3 expression ( 6 ). The low abundance could be observed using several primer pairs, as these produced high Cq values, irregular melting peaks, and gel electrophoresis did not show a specific primer product in 55% of samples ( Supplementary Figure 3 ).…”

“…T-regulatory cells exhibit immunosuppressive capabilities and infer immunologic tolerance to auto- and alloantigens ( 4 , 5 ). In kidney transplant recipients, studies have shown that recipients with higher levels of T-regulatory cells are less likely to experience allograft rejection, and that recipients with higher levels of FOXP3 show stable allograft function despite negligible immunosuppressive therapy ( 6 ). Moreover, FOXP3 levels are altered by immunosuppressive therapy ( 6 ) and could mirror a recipient’s degree of immunosuppression.…”

“…In kidney transplant recipients, studies have shown that recipients with higher levels of T-regulatory cells are less likely to experience allograft rejection, and that recipients with higher levels of FOXP3 show stable allograft function despite negligible immunosuppressive therapy ( 6 ). Moreover, FOXP3 levels are altered by immunosuppressive therapy ( 6 ) and could mirror a recipient’s degree of immunosuppression. A few studies have measured FOXP3 mRNA levels in kidney transplant recipients, but these did not include the different FOXP3 splice variants ( 7 , 8 ).…”

CDC42—a promising target of glioma treatment related to Treg cell proliferation

“…CDC42 is associated with the development of Treg cells in the tumor microenvironment. According to the literature, Treg cells play an indispensable role in tumor immune evasion, The correlation between CDC42 expression in glioma and three markers of Treg cells (CD4, IL2RA (CD25), IL7R (CD127)) 21 (Figrue9) was explored by person correlation analysis using Stata software, the results showed that CDC42 expression correlated with CD4 (r=0.552, p<0.001), IL2RA (r=0.560, p<0.001) in the TCGA database. The expression results of CD4 (r=0.326, p<0.001), IL2RA (r=244, p<0.001), IL7R (r=447, p<0.001) were demonstrated in the CGGA database, and the level of CDC42 expression may be related to the effectiveness of immunotherapy.…”