Expansion of a restricted residual host Treg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation

We previously identified a population of residual T-reg cells following autologous hematopoietic stem transplantation (HSCT), that rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived T-reg cells. These CD4(+)Foxp3(+) T cells provide protection from the development of autoimmune disease. Although ablative conditioning results in excess IL-7 and IL-15, IL-2 is typically not found at high levels following autologous HSCT. We therefore examined the role of these three STAT-5 signaling cytokines in the expansion of residual T-reg cells after autologous HSCT. The present study found that the residual T-reg cell population included surviving peripheral host Foxp3(+)CD4(+) T cells whose expansion was critically dependent on IL-2, which could be solely provided by surviving host cells. IL-7 was found to contribute to T-reg cell homeostasis, however, not as a growth factor but rather for their persistence. In conjunction with this expansion, TCR spectratype analyses revealed that the residual host T-reg-cell compartment differed from that present in non-conditioned healthy mice since the residual host T-reg cells exhibit a limited TCR diversity. Collectively, these data indicate that the proliferation of T-reg and T effector (T-eff) cells post-HSCT utilize separate pools of cytokines which has important implications regarding the development of clinical strategies to elicit the desired immune responses in patients post-transplant.