Expansion of a restricted residual host T sub(reg)-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation

• Published in: European journal of immunology 2011-12, Vol.41 (12), p.3467-3478
• Main Authors: Bayer, Allison L, Chirinos, Jackeline, Cabello, Cecilia, Yang, Jing, Matsutani, Takaji, Malek, Thomas R, Levy, Robert B
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141611

We previously identified a population of residual T sub(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 sub(reg) cells. These CD4 super(+)Foxp3 super(+) 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 sub(reg) cells after autologous HSCT. The present study found that the residual T sub(reg) cell population included surviving peripheral host Foxp3 super(+)CD4 super(+) 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 sub(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 sub(reg)-cell compartment differed from that present in non-conditioned healthy mice since the residual host Treg cells exhibit a limited TCR diversity. Collectively, these data indicate that the proliferation of T sub(reg) and T effector (T sub(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.