PMID- 15327522 OWN - NLM STAT- MEDLINE DCOM- 20041101 LR - 20061115 IS - 0007-1048 (Print) IS - 0007-1048 (Linking) VI - 126 IP - 5 DP - 2004 Sep TI - Kinetic of regulatory CD25high and activated CD134+ (OX40) T lymphocytes during acute and chronic graft-versus-host disease after allogeneic bone marrow transplantation. PG - 697-703 AB - 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. FAU - Sanchez, Joaquin AU - Sanchez J AD - Haematology Department and Bone Marrow Transplantation Unit, University Hospital Reina Sofia, 14004 Cordoba, Spain. joaquin.sanchez@cheerful.com FAU - Casano, Javier AU - Casano J FAU - Alvarez, Miguel A AU - Alvarez MA FAU - Roman-Gomez, Jose AU - Roman-Gomez J FAU - Martin, Carmen AU - Martin C FAU - Martinez, Francisco AU - Martinez F FAU - Gomez, Pedro AU - Gomez P FAU - Serrano, Josefina AU - Serrano J FAU - Herrera, Concepcion AU - Herrera C FAU - Torres, Antonio AU - Torres A LA - eng PT - Journal Article PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Receptors, Interleukin-2) RN - 0 (Receptors, OX40) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (TNFRSF4 protein, human) SB - IM MH - Acute Disease MH - Adolescent MH - Adult MH - *Bone Marrow Transplantation MH - Child MH - Child, Preschool MH - Chronic Disease MH - Female MH - Graft vs Host Disease/*immunology MH - Humans MH - Lymphocyte Activation MH - Male MH - Middle Aged MH - Prospective Studies MH - Receptors, Interleukin-2/*immunology MH - Receptors, OX40 MH - Receptors, Tumor Necrosis Factor/*immunology MH - Regression Analysis MH - T-Lymphocytes/*immunology MH - Transplantation Immunology MH - Transplantation, Homologous EDAT- 2004/08/26 05:00 MHDA- 2004/11/02 09:00 CRDT- 2004/08/26 05:00 PHST- 2004/08/26 05:00 [pubmed] PHST- 2004/11/02 09:00 [medline] PHST- 2004/08/26 05:00 [entrez] AID - BJH5108 [pii] AID - 10.1111/j.1365-2141.2004.05108.x [doi] PST - ppublish SO - Br J Haematol. 2004 Sep;126(5):697-703. doi: 10.1111/j.1365-2141.2004.05108.x.