title: Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation.
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.
authors.affiliation: Department of Transfusion Medicine and Transplantation Immunology, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima, Fukushima 960-1295, Japan.
authors.forename: Alain M
authors.initials: AM
authors.lastname: Ngoma
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Sano
authors.forename: Hayato
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Noji
authors.forename: Syunnichi
authors.initials: S
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kikuta
authors.forename: Kazuei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Mikio
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Nollet
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohto
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D014184:Transplantation, Homologous; D055815:Young Adult