Regulatory T Cells and T Cell Depletion

Abstract

؉ CD25 high cells that expressed FOXP3 underwent homeostatic peripheral expansion during immune reconstitution, more intense in patients who received sirolimus than in those who were given CsA. T cells that were isolated from peripheral blood long term after transplantation were hyporesponsive to alloantigens in both groups. In sirolimus-but not CsA-treated patients, hyporesponsiveness was reversed by Treg depletion. T cells from CsA-treated patients were anergic. Thus, lymphopenia and calcineurin-dependent signaling seem to be primary mediators of CD4 ؉ CD25 high Treg expansion in renal transplant patients. These findings will be instrumental in developing "tolerance permissive" immunosuppressive regimens in the clinical setting.

Achieving Donor-Specific Hyporesponsiveness Is Associated with FOXP3+ Regulatory T Cell Recruitment in Human Renal Allograft Infiltrates

“…In addition, these Tregs exhibited donor-Ag specificity, because they were capable of abrogating cytokine production against their paired donor when transferred to an allogenic HLA-mismatch responder individual. In accordance to our data, Noris et al (16) recently showed a significantly higher expansion of FOXP3 ϩ CD4 ϩ CD25 ϩhigh Tregs using alemtuzumab as a T cell depletion agent followed by SRL and MMF compared with alemtuzumab, CNI, and MMF. They demonstrated that donor-specific hyporesponsiveness achievement in the SRL group was due to the expansion and suppressive activity of these Tregs, instead of the induction of an anergic state in the CNI-treated group.…”

Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

“…17 It has been described that some immunosuppressants such as SRL and rATG are more likely to play a role in the development and expansion of Treg in peripheral blood. 16,23 Furthermore, a recent interesting experimental report showed how SRL induced expression of TGF-␤ played a role in the recruitment of FoxP3 ϩ Treg from the naive pool whereas CNI have an opposite effect and prevent recruitment of Treg. 24 Here, we also show for the first time that patients who are on SRL and/or are receiving induction therapy (mostly with rATG) have significantly higher expression of FoxP3 ϩ Treg within clinically stable renal allografts.…”

Functional plasticity in human FOXP3+regulatory T cells

“…22 Approaches selectively favoring the survival of Treg cells include the provision of low doses of IL-2, or the use of immunosuppressive pharmaceutical agents such as Cyclosporin A and Rapamycin, which have recently been found to selectively modulate biochemical pathways in Tconv or Treg cells. 23 Helpful in human hematopoietic stem cell transplantation, these approaches have so far only been proven beneficial for autoimmunity in mice. 24,25 The infusion of Treg cells is the second main type of therapy pursued in humans.…”