Abstract
<div>Abstract<p>Compelling evidences indicate a key role for regulatory T cells (T<sub>reg</sub>) on the host response to cancer. The Wilms' tumor antigen (WT1) is overexpressed in several human leukemias and thus considered as promising target for development of leukemia vaccine. However, recent studies indicated that the generation of effective WT1-specific cytotoxic T cells can be largely affected by the presence of T<sub>regs</sub>. We have generated T-cell lines and clones that specifically recognized a WT1-84 (RYFKLSHLQMHSRKH) peptide in an HLA-DRB1*0402–restricted manner. Importantly, they recognized HLA-DRB1*04–matched fresh leukemic cells expressing the WT1 antigen. These clones exerted a T helper 2 cytokine profile, had a CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>GITR<sup>+</sup>CD127<sup>−</sup> T<sub>reg</sub> phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact. Priming of alloreactive T cells in the presence of T<sub>regs</sub> strongly inhibited the expansion of natural killer (NK), NK T, and CD8<sup>+</sup> T cells and had an inhibitory effect on NK/NK T cytotoxic activity but not on CD8<sup>+</sup> T cells. Furthermore, priming of T cells with the WT1-126 HLA-A0201–restricted peptide in the presence of T<sub>regs</sub> strongly inhibited the induction of anti–WT1-126 CD8<sup>+</sup> CTL responses as evidenced by both very low cytotoxic activity and IFN-γ production. Moreover, these T<sub>reg</sub> clones specifically produced granzyme B and selectively induced apoptosis in WT1-84–pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells. Importantly, we have also detected anti–WT1-84 interleukin-5<sup>+</sup>/granzyme B<sup>+</sup>/Foxp3<sup>+</sup> CD4<sup>+</sup> T<sub>regs</sub> in five of eight HLA-DR4<sup>+</sup> acute myeloid leukemia patients. Collectively, our <i>in vitro</i> and <i>in vivo</i> findings strongly suggest important implications for the clinical manipulation of T<sub>regs</sub> in cancer patients. [Cancer Res 2008;68(15):6350–9]</p></div>
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
