Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation

To elucidate the correlation between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) or cytomegalovirus infection following allogeneic bone marrow transplantation (allo-BMT), we evaluated either CD4+CD25high or FOXP3+ Treg-enriched cells in peripheral blood (PB) from 20 patients who received allo-BMT, and in biopsies of skin with aGVHD. Proportions of CD4+CD25highFOXP3+ cells in total lymphocytes, but not other types of T cells, were lower in patients who eventually developed grades II–IV aGVHD (n = 13) than in others (n = 7, P < 0.001). Proportions of CD62L+ cells in CD4+CD25high cells at day +30 were lower (P < 0.01) in patients who eventually showed cytomegalovirus viremia (n = 6) than in others (n = 14). Incidence of aGVHD (P < 0.05) or cytomegalovirus viremia (P < 0.05) was higher in patients without these complications, but with lower proportions of PB CD4+CD25highFOXP3+ cells at day +30 (n = 8) than in others (n = 8). However, in skin with aGVHD (n = 5), there was marked or slightly increased infiltration of CD8+ cells (P < 0.001) or CD3+FOXP3+ cells (P < 0.05), respectively, when compared with control (n = 5), resulting in threefold higher ratio of CD8+/CD3+FOXP3+ cells in aGVHD relative to controls (P < 0.05). Thus, impaired reconstitution of Tregs may be associated with aGVHD and CMV infection. Moreover, imbalance of Tregs and CD8+ cells may play a role in aGVHD tissue.