Abstract
Adoptive regulatory T cell (Treg) trasfer represents a potential
therapeutic option to control immune responses in organ transplantation,
graft vs host disease, and autoimmunity, including type 1 diabetes. Treg
for adoptive therapy are traditionally sorted and expanded in
vitro with high doses of IL-2, showing stability and suppressive
capacity, but with some limitations in terms of long-term survival once
infused in patients. Here, we tested a novel expansion protocol in which
we added IL-7 (IL-7 method, IL-7M) to the traditional standard method
(StM) using IL-2. We showed that naïve Treg express significant levels
of CD127 and robustly respond to IL-7 by phosphorylating STAT-5. Naive
Treg expanded with the IL-7M were highly enriched in CD45RA
+CD62L +CD95 +
showing a reduction in the final cell yield and suppressive function.
Treg expanded with the IL-7M preserved telomere length and were more
resistant to cytokine withdrawal and fas-mediated apoptosis. Overall our
data indicate that it is possible to expand naïve Treg in the presence
of IL-7 to generate a final Treg product enriched in poorly
differentiated CD45RA + cells and with better
resistance to stress and apoptosis, potentially improving the long-term
survival of Treg in adoptive transfer protocols.