CD8 membrane expression is down-regulated by transforming growth factor (TGF)beta 1, TGF-beta 2, and prostaglandin E2

PROBLEM: CD8 T-cells are present at a lower frequency in human decidua than in peripheral blood. Because transforming growth factor (TGF)-beta 2 down- regulates CD4 membrane expression, its contribution, as well as the contrib ution of TGF-beta 1 and prostaglandin (PG) E2, to the modulation CDS expres sion was studied using human peripheral blood lymphocytes (PBLs). METHOD OF STUDY: PBLs were cultured with TGF-beta 1, TGF-beta 1, PGE 2, PGI 2, or day-12 rabbit blastocoelic fluid (BF) that was or was not depleted o f TGF-beta 2 and/or PGE 2. Quantum Simply Cellular Microbeads(TM) were then used to evaluate CD8 membrane expression levels. RESULTS: This study is the first demonstration that treatment of PBLs with TGF-beta 1, TGF-beta 2, and PGE 2 leads to a dose-dependent decrease in CD8 expression. A significant inhibition was observed at 2.5 ng/mL for TGF-bet a 2, 5 ng/mL for TGF-beta 1, and 10 ng/mL for PGE 2. In contrast, PGI 2 had no effect. Treatment of PBLs with BF day-12 decreased CD8 expression. This effect, however, was not observed when BF was depleted of TGF-beta 2 and/o r PGE 2. CONCLUSIONS: Our results suggest that TGF-beta s and PGE 2 are important mo dulators of CDS membrane expression in human lymphocytes. Because TGF-beta 1, TGF-beta 2, and PGE 2 are produced by the conceptus and by uterine cells , and because the effect is observed after only 3 days of treatment, the pr esent data suggest that these substances can locally modulate the phenotype of lymphocytes at the fetomaternal interface. Such modulation may explain. at least partly. the changes observed in the population of decidual lympho cytes during pregnancy.