CD4+ T cells in aged or thymectomized recipients of allogeneic stem cell transplantations

Hiroshi Takahashi, Kazuhiko Ikeda, Kazuei Ogawa, Syunnichi Saito, Alain M Ngoma, Yumiko Mashimo, Koki Ueda, Miki Furukawa, Akiko Shichishima-Nakamura, Hiroshi Ohkawara, Kenneth E Nollet, Hitoshi Ohto, Yasuchika Takeishi

CD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus-derived and peripherally induced cells, play a central role in immune regulation, and are therefore crucial to prevent graft-versus-host disease (GVHD). The increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with thymus regression, and our case of allo-HSCT shortly after total thymectomy, raised questions about the activity of thymus-derived Treg cells and peripherally induced Treg cells, which are otherwise indistinguishable. We found that despite pre-transplant thymectomy or older age, both naïve and effector Treg cells, as well as naïve and effector conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of total Treg cells 1 month post allo-HSCT, and naïve Treg cells 1 year post allo-HSCT, appeared in patients achieving complete chimera without developing significant chronic GVHD, including our thymectomized patient, compared with patients who developed chronic GVHD. Treg cells that modulate human allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT recipients.