Depletion of CD4+CD25+ human regulatory T cells in vivo: Kinetics of Treg depletion and alterations in immune functions in vivo and in vitro

摘要: The aim of this study was to investigate whether depletion CD4(+)CD25(+) regulatory T cells (Treg) from melanoma patients affects immune responses against tumors. By application recombinant IL-2-diphteria toxin fusion protein, also known as ONTAK, we were able significantly reduce the frequency Treg in peripheral blood, whereas other cell populations remained unaffected. reduction started immediately after first bolus ONTAK with a dose 5 microg per kg bodyweight and lasted for 13 days subsequent recovery thereafter. Successive treatments further reduced number circulating Treg. Using contact sensitizer DCP show that all developed vast eczema depletion, no or only mild eczematous reactions detectable before treatment. Corresponding induction DCP-specific CD4(+) CD8(+) detectable. Moreover, immunization treated tumor antigen peptides, MelanA/MART-1 gp100, significant peptide specific could be observed 90% treated. These displayed effector functions, they lyse peptide-pulsed target secreted IFNgamma upon restimulation. In aggregate, our data indicate depletes vivo significantly, resulting enhanced functions substantial development antigen-specific vaccinated individuals.