Submitted February 24, 2006
Accepted June 28, 2006
Naive regulatory T cells: a novel subpopulation defined by resistance towards CD95L-mediated cell death
Benedikt Fritzsching, Nina Oberle, Eva Pauly, Robert Geffers, Jan Buer*, Johannes Poschl, Peter Krammer, Otwin Linderkamp, and Elisabeth Suri-Payer
Department of Neonatology, Children's Hospital, University of Heidelberg, Germany
Divsion of Immunogenetics, German Cancer Research Center, Heidelberg, Germany
Department of Mucosal Immunity, German Research Center for Biotechnology, Braunschweig, Germany
* Corresponding author; email: jan.buer{at}gbf.de.
The majority of CD4+CD25hiFOXP3+ regulatory T cells (Treg) from adult peripheral blood expresses high levels of CD45RO and CD95 and is prone to CD95L-mediated apoptosis in contrast to conventional T cells (Tconv). However, a Treg subpopulation remained consistently apoptosis-resistant. Gene micro array and 6-color flow cytometry analysis including FOXP3 revealed an increase in naive T cell markers on the CD95L-resistant Treg compared to the majority of Treg. In contrast to Treg found in adult humans, most CD4+CD25+FOXP3+ T cells found in cord blood are naive and exhibit low CD95 expression. Furthermore, the great majority of these newborn Treg is not sensitive towards CD95L similar to naive Treg from adult individuals. After short-time stimulation with anti-CD3/28 mAbs cord blood Treg strongly upregulated CD95 and were sensitized towards CD95L. This functional change was paralleled by a rapid upregulation of memory T cell markers on cord blood Treg that are frequently found on adult memory Treg. In summary, we show a clear functional difference between naive and memory Treg that could result in different survival rates of those two cell populations in vivo. This new observation could be crucial for the planning of therapeutic application of Treg.
