CD4+CD25+ immunoregulatory T cells play a pivotal role in preventing organ-specific autoimmune diseases and in tolerance induction to allogeneic organ transplants. We investigated whether these cells could also control graft-versus-host disease (GVHD), the main complication after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we show that the few CD4+CD25+ T cells naturally present in the transplant regulate GVHD because their removal from the graft dramatically accelerates this disease. Furthermore, the addition of freshly isolated CD4+CD25+ T cells at time of grafting significantly delays or even prevents GVHD. Ex vivo–expanded CD4+CD25+ regulatory T cells obtained after stimulation by allogeneic recipient-type antigen-presenting cells can also modulate GVHD. Thus, CD4+CD25+ regulatory T cells represent a new therapeutic tool for controlling GVHD in allogeneic HSCT. More generally, these results outline the tremendous potential of regulatory T cells as therapeutics.
Intra-uterine pressure was recorded by placing a Foley catheter in the extra-amniotic space before the termination of pregnancy in 25 patients, and Caesarean section in 12 patients. The effects of administration of i.v. ketamine 2 mg/kg body weight, sodium thiopentone 4 mg/kg body weight and ergometrine 0.5 mg, and intra-cervical 0.5% lignocaine 20 ml were measured in the first trimester of pregnancy, and i.v. ketamine and sodium thiopentone in late pregnancy. Ketamine was found to cause uterine contraction (mean increase 16.1 mm Hg) equal to ergometrine (mean increase 14.8 mm Hg) in early pregnancy, but exert no effect (mean decrease -- 1.33 mm Hg) in late pregnancy. Lignocaine in early pregnancy given as a paracervical block had no significant effect on intrauterine pressure (mean increase 0.33 mm Hg). Sodium thiopentone (mean decrease -- 4.28 mm Hg first trimester and -- 2.22 mm Hg at term) in late pregnancy had no significant effect on intra-uterine pressure.
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