Interleukin-15 enhances CD4(+) CD45RA(+) expression on umbilical cord blood mononuclear cells.
The reduced incidence of graft-vs.-host disease following umbilical cord blood (CB) transplantation may be related to the functional immaturity of newborn T cells expressing mainly the naive CD45RA phenotype. Expansion of CD4(+) CD45RA(+) T cells using cytokines may benefit neonates and infants with human immunodeficiency virus (HIV) infection, as a preferential decline in CD4(+) CD45RA(+) cells has been noted as HIV disease progresses. The aim of the study was to investigate the effect of interleukin (IL)-15, a novel cytokine similar to IL-2 in biological activities, on CD45RA/RO expression and apoptosis in umbilical cord blood (CB) and adult peripheral blood (APB) mononuclear cells (MNCs). Prior to culture, CB MNCs contained a greater number of CD4(+) CD45RA(+) cells and fewer CD4(+) CD45RO(+) cells than did APB MNCs. When incubated with RPMI-1640 containing 10% fetal calf serum for 7 days, the percentage of CD45RA(+) cells within CD4(+) T cells (%CD45RA(+)/CD4(+)) significantly decreased compared to that of fresh CB MNCs. IL-15 exerted a dose-dependent increase of %CD45RA(+)/CD4(+) and a corresponding decrease of %CD45RO(+)/CD4(+) in CB MNCs, an effect not observed with APB MNCs treated with IL-15. The percentages of CD45RA(+) and CD45RO(+) expression within CD8(+) cells, however, were not influenced by IL-15, in either CB or APB MNCs. A greater number of CB MNCs underwent apoptosis than did APB MNCs after 7 days of culture in RPMI-1640 containing 10% fetal calf serum. IL-15 did not inhibit apoptosis but induced proliferation comparable to that achieved in APB MNCs. The ability of IL-15 to preferentially enhance the proliferation of CD4(+) CD45RA(+) cells in CB MNCs suggests a role for immunomodulative therapy in HIV-infected newborns and infants.
Lin
S J
SJ
Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan, China. sjlino@adm.cgmh.org.tw
Chao
H C
HC
D000328:Adult; D017209:Apoptosis; D015704:CD4 Antigens / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D005312:Fetal Blood; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D019409:Interleukin-15 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*
D015704:CD4 Antigens; D019409:Interleukin-15; D017493:Leukocyte Common Antigens