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Cord Blood Stem Cells

Effect of interleukin (IL)-12 and IL-15 on apoptosis and proliferation of umbilical cord blood mononuclear cells

Abstract

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. Bone Marrow Transplantation (2001) 28, 439–445.

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Acknowledgements

This study was supported by grants from National Science Council in Taiwan (NSC 88-2314-B-182A-028 and NSC 88-2314-B-182A-040), and Chang Gung Memorial Hospital (CMRP704).

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Lin, SJ., Wang, LY., Huang, YJ. et al. Effect of interleukin (IL)-12 and IL-15 on apoptosis and proliferation of umbilical cord blood mononuclear cells. Bone Marrow Transplant 28, 439–445 (2001). https://doi.org/10.1038/sj.bmt.1703182

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