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

Int J Hematol. 2012 Jan;95(1):86-94. doi: 10.1007/s12185-011-0976-7. Epub 2011 Dec 14.

Abstract

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⁺CD25(high) 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⁺CD25(high)FOXP3⁺ 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⁺CD25(high) 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⁺CD25(high)FOXP3⁺ 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.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Bone Marrow Transplantation / immunology*
  • Child
  • Child, Preschool
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / immunology*
  • Female
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / virology
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / virology
  • Transplantation, Homologous
  • Young Adult