Differential effect of IL‐15 and IL‐2 on survival of phytohemagglutinin‐activated umbilical cord blood T cells

• Published in: American journal of hematology Vol. 80; no. 2; pp. 106 - 112
• Main Authors: Lin, Syh‐Jae, Cheng, Po‐Jen, Hsiao, Shiu‐Shan, Lin, Hui‐Hao, Hung, Pei‐Fen, Kuo, Ming‐Ling
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2005; Wiley-Liss
• Subjects: apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspase 3; Caspases - analysis; Cell Survival - drug effects; cord blood; Fetal Blood - cytology; Hematologic and hematopoietic diseases; Humans; Interleukin-12 - pharmacology; Interleukin-15 - pharmacology; interleukin‐15; interleukin‐2; Lymphocyte Activation - drug effects; Medical sciences; Phytohemagglutinins - pharmacology; Proto-Oncogene Proteins c-bcl-2 - analysis; Receptors, Interleukin-15; Receptors, Interleukin-2 - deficiency; T cells; T-Lymphocytes - cytology; TNF‐α; cord blood; interleukin-2; Hematology; Cytokine; Phytohemagglutinin; Interleukin 15; T cells; Survival; Blood; interleukin-15; Blood cell; Interleukin 2; TNF-α; Cell death; T-Lymphocyte; Umbilical cord; Tumor necrosis factor α; Apoptosis
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.20431

Cytokine immunotherapy using interleukin (IL)‐2 and IL‐15 may be beneficial for patients receiving umbilical cord blood (CB) transplantation by ameliorating post‐transplant T‐cell apoptosis. The present study compares the differential effect of IL‐15 and IL‐2 on survival of phytohemagglutinin (PHA)‐activated CB and adult peripheral blood (APB) T lymphocytes. In comparison with IL‐2, IL‐15 preferentially enhanced the survival of CB PHA‐activated T cells by decreasing the caspase‐3+ population and by increasing the Bcl‐2+ population. Activated CB T cells were more susceptible to TNF‐α‐induced apoptosis compared to their adult counterparts. However, the susceptibility could be abrogated by IL‐15 but not by IL‐2. IL‐15 but not IL‐2 down‐regulated CD28 expression on both activated CB and APB CD8+ T cells, with a much greater effect seen with CB. Western‐blot analysis shows that IL‐15 Rα is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL‐15 significantly enhanced CB IL‐15 Rα expression to levels comparable to that of adults. Thus, IL‐15 may provide a better therapeutic choice for immune reconstitution than IL‐2 post‐CB transplantation due to its preferential survival enhancing effect on CB T cells. Am. J. Hematol. 80:106–112, 2005. © 2005 Wiley‐Liss, Inc.