Differential effect of IL-15 and IL-2 on survival of phytohemagglutinin-activated umbilical cord blood T cells.
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-alpha-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 Ralpha is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL-15 significantly enhanced CB IL-15 Ralpha 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.
Lin
Syh-Jae
SJ
Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Cheng
Po-Jen
PJ
Hsiao
Shiu-Shan
SS
Lin
Hui-Hao
HH
Hung
Pei-Fen
PF
Kuo
Ming-Ling
ML
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000172:deficiency; D013601:T-Lymphocytes / Q000166:cytology*
C508024:IL15RA protein, human; D019409:Interleukin-15; D010835:Phytohemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases