Kinetic of regulatory CD25high and activated CD134+ (OX40) T lymphocytes during acute and chronic graft-versus-host disease after allogeneic bone marrow transplantation.
Graft-versus-host disease (GVHD) is still a major complication after allogeneic stem cell transplantation. In murine models, freshly isolated or ex vivo expanded CD4(+)CD25(high) regulatory T cells (Treg) are able to ameliorate GVHD while maintaining graft-versus-leukaemia reactions. However, in the human setting, prospective studies of this population and its interaction with activated non-regulatory CD134(+) (OX40) lymphocytes during post-transplant follow-up are lacking. In this study, we prospectively quantified CD4(+)CD25(high) and activated CD134(+) lymphocytes in 119 peripheral blood samples from 35 consecutive patients who underwent allogeneic bone marrow transplantation (BMT). Fifty-five samples obtained less than 100 d after allogeneic BMT, were not statistically different regarding CD4(+)CD25(high) Treg or CD134(+) lymphocytes compared with those obtained from patients with (n = 35) or without (n = 20) acute GVHD. Chronic GVHD was associated with a small, but not statistically significant, increase in the number of Treg (9.9 vs. 6.7 x 10(6)/L). However, the CD134/CD25(high) ratio was significantly higher during chronic GVHD (cGHVD) when compared with either patients without cGVHD (67.7 +/- 40.3 vs. 4.0 +/- 0.9, P < 0.01) or cGVHD after treatment (67.7 +/- 40.3 vs. 3.7 +/- 0.8, P < 0.01). Our findings suggest that the suppressive activity of CD4(+)CD25(high) Treg could be abrogated in vivo during cGVHD by CD134 expression in a much higher number of activated donor T lymphocytes. In addition to CD4(+)CD25(high)ex vivo expansion protocols, OX40 blocking might be crucial to optimize the use of Treg to prevent GVHD.
Haematology Department and Bone Marrow Transplantation Unit, University Hospital Reina Sofía, 14004 Cordoba, Spain. joaquin.sanchez@cheerful.com
Joaquin
J
Sanchez
Javier
J
Casaño
Miguel A
MA
Alvarez
Jose
J
Roman-Gomez
Carmen
C
Martin
Francisco
F
Martinez
Pedro
P
Gomez
Josefina
J
Serrano
Concepcion
C
Herrera
Antonio
A
Torres
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human