Summary:In this study, the immunity of umbilical cord blood (UCB) T lymphocytes against allo-antigens was investigated by a standard MLC. No significant difference, between the UCB T cells or peripheral blood (PB) mature T cells, was observed in the primary responses (stimulation index (SI), 51.8 ؎ 14.8 and 46.5 ؎ 15.0, respectively). In contrast, in the secondary response, the SI obtained with the CD4 T cells from UCB decreased dramatically (16.3 ؎ 6.4), while it increased with the CD4 T cells from PB (118.5 ؎ 21.7). UCB (CD4 and CD8) T cells separately showed much higher frequencies of apoptosis after a primary allo-priming, compared with PB CD4 and CD8 T cells (CD4, UCB 30.5% vs PB 0.8%; CD8, UCB 32% vs PB 1.3%). The higher apoptotic level of the UCB CD4 T cells was confirmed by a second, ELISA-based, Tunel assay (OD values, UCB CD4 1.93 ؎ 0.31 vs PB CD4 0.59 0.9; P Ͻ 0.01). Those apoptotic steps were not attributed to the amount of cytokine (IL-2, 4 and IFN-gamma) production, which was found to be similar in both cases. In conclusion, UCB lymphocytes are much more likely to be induced to apoptosis by allo-priming than adult lymphocytes. This supports their possible, successful engraftment across barriers of HLA incompatibility. Keywords: cord blood; MLR; apoptosis Human umbilical cord blood (UCB) is considered to be a good source of stem cells for transplantation, especially in BM insufficiency or malignant hematological disorders such as leukemia. [1][2][3][4][5] The unique nature of UCB is its immunological immaturity, which should contribute to a low incidence of GVHD in allogeneic stem cell transplantation. 5 Much research has been conducted to clarify the characteristics of UCB lymphocytes. In summary, it has been reported that UCB has fewer CD3-positive T lymphocytes, 6-10 among which the majority express the naive, nonprimed CD45RA marker, and express fewer IL-2 receptor Correspondence: Dr M Hagihara, Department of Hematology and Rheumatology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan Received 29 April 1999; accepted 18 July 1999 molecules than adult PBL. 8 However, there is controversy about the immunoreactivity of UCB lymphocytes against allo-antigens. [11][12][13][14][15][16] While the majority of studies demonstrated that UCB lymphocytes have a lower proliferative potential than BM or PB lymphocytes, 11-13 others argue against that theory and have reported that UCB T lymphocytes have a potential to proliferate as strongly as PB T lymphocytes. [14][15][16] Several recent studies further examined the immunological nature of UCB or neonatal lymphocytes and showed that programmed cell death (apoptosis) is a key phenomenon for immunological tolerance or anergy. [17][18][19] Compared with PBL, the UCB cells were resistant to apoptosis upon stimulation with anti-CD3 MoAb. However, when challenged repeatedly, they were triggered to apoptosis. 20 With this background, we conducted a study to observe not only primary, but also secondary allo-response of UCB T cells, t...