Effect of interleukin (IL)-12 and IL-15 on apoptosis and proliferation of umbilical cord blood mononuclear cells.
Decreased graft-versus-host disease (GVHD) in cord blood (CB) transplantation may be attributed to the immunological immaturity and susceptibility to apoptosis of CB mononuclear cells (MNCs). Cytokines like interleukin (IL)-12 and IL-15 may be used for in vivoadministration or ex vivo expansion of lymphoid cells for more rapid recovery following stem cell transplant, and for providing a graft-versus-leukemia (GVL) effect. We investigated the effects of IL-12 and IL-15, alone or in combination on apoptosis and proliferation of both CB and adult peripheral blood (APB) MNCs, with particular emphasis on CB CD4+, CD8+ and CD56+ lymphocyte subpopulations. The results of our study indicated that: (1) the combination of IL-12+IL-15 resulted in a greater degree of CB and APB apoptosis than either cytokine alone; (2) the level of both spontaneous and cytokine-induced apoptosis by IL-12 and/or IL-15 are greater in CB MNCs than in APB MNCs using TUNEL assays; (3) IL-15 is superior to IL-12 in enhancing the proliferative response in CB and APB MNCs; (4) the combination of IL-12+IL-15, but not either cytokine alone, significantly enhanced apoptosis in CD8+ and CD56+ CB subsets, but not in CD4+ CB subsets; (5) IL-12 or IL-15 alone resulted in increased proliferation in CD4+, CD8+ and CD56+ CB subsets, with IL-12+IL-15 producing the greatest increase of proliferation in all three CB subsets; and (6) IL-15 and/or IL-12 significantly upregulate Fas (CD95) expression on CB T and NK cells. These findings may have therapeutic implications when designing cytokine therapy in patients receiving CB transplant.
Lin
S J
SJ
Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan, Taiwan.
Wang
L Y
LY
Huang
Y J
YJ
Kuo
M L
ML
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D019002:CD56 Antigen / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007231:Infant, Newborn; D018664:Interleukin-12 / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D011419:Propidium / Q000378:metabolism; D013194:Staining and Labeling; D019014:fas Receptor / Q000096:biosynthesis
D017252:CD3 Complex; D019002:CD56 Antigen; D019409:Interleukin-15; D019014:fas Receptor; D018664:Interleukin-12; D011419:Propidium