Effect of interleukin-15 on anti-CD3/anti-CD28 induced apoptosis of umbilical cord blood CD4+ T cells.
OBJECTIVE
Interleukin-15 (IL-15) has potential therapeutic advantage for patients receiving umbilical cord blood (CB) transplantation. The present study aims to examine the ability of IL-15 to modulate the survival, maturation, and function of anti-CD3/anti-CD28 stimulated CB CD4+ T cells, in comparison with responses from adult peripheral blood (APB) CD4+ T cells.


METHODS
Enriched CB and APB CD4+ T cells were stimulated with anti-CD3 and anti-CD28 (anti-CD3/anti-CD28) in the presence or absence of IL-15 (10 ng/mL) for 5 d. The percentages of apoptotic cells were assessed by propidium iodide/annexin-V flow cytometric staining. T-cell activation was analyzed with the expression of surface markers (CD45RO/CD69/CD25). Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) production in culture supernatant was determined by enzyme-linked immunosorbent assay.


RESULTS
CB CD4+ T cells had a higher survival and lower apoptotic response following anti-CD3/anti-CD28 stimulation, compared with APB CD4+ T cells. IL-15 enhanced apoptosis and promoted CD45RO conversion of anti-CD3/anti-CD28 activated CB CD4+ T cells, an effect not observed with APB CD4+ T cells. Although activated CB CD4+ T cells expressed comparable level of CD69/CD25 expression to adults, IFN-gamma production of activated CB CD4+ T cells was markedly deficient compared with that of corresponding APB CD4+ T cells. Exogenous IL-15 further enhanced the production of IFN-gamma, but not TNF-alpha, of activated CB CD4+ T cells.


CONCLUSIONS
IL-15 preferentially resulted in an activation-enhancing effect on CB CD4+ T cells, accompanied by increased apoptosis. Our finding may have therapeutic implications while designing IL-15 immunotherapy for patients receiving CB transplant.
Lin
Syh-Jae
SJ
Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Yu
Jung-Chuan
JC
Cheng
Po-Jen
PJ
Hsiao
Shiu-Shan
SS
Kuo
Ming-Ling
ML
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018106:CD28 Antigens / Q000276:immunology* / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002470:Cell Survival; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens