Functional analyses of cord blood natural killer cells and T cells: a distinctive interleukin-18 response.
OBJECTIVE
To search for the functional property of cord blood (CB) cells, the effects of interleukin-18 (IL-18) on interferon-gamma (IFN-gamma) production of T cells or natural killer (NK) cells were compared between CB and adult peripheral blood (PB).


METHODS
T cells, CD45RA(+) T cells, and NK cells were purified from CB and adult PB mononuclear cells using magnetic beads or a cell sorter. After stimulation with or without IL-18 in the presence of IL-12 for 48 hours (NK cells) or 72 hours (T cells or CD45RA(+) T cells), IFN-gamma concentration was measured in each subset. Although IL-18 induced significant IFN-gamma production from both CB and adult PB T cells in the presence of IL-12, the IFN-gamma levels from CB T cells were lower than those from adult PB T cells. However, CD45RA(+) T cells from CB and from adult PB produced similar levels of IFN-gamma after stimulation with IL-18 + IL-12. On the other hand, CB NK cells exhibited higher IFN-gamma production and CD69 expression than adult PB NK cells after stimulation with IL-18 + IL-12. Cytolytic activity of CB NK cells increased to a level comparable to that of adult PB NK cells after the same IL-18/IL-12 stimulation.


CONCLUSIONS
These results suggest that a low response of CB T cells to IL-18 is due to a higher proportion of naive (CD45RA(+)) T cells in CB, which may be one of the factors responsible for the neonatal immaturity of the immune system as well as the low incidence of graft-vs-host disease in patients receiving CB stem cell transplantation. On the other hand, a high response of CB NK cells to IL-18 may contribute to the host defense during the neonatal period and antitumor effects in CB stem cell transplantation.
Nomura
A
A
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. anomura@pediatr.med.kyushu-u.ac.jp
Takada
H
H
Jin
C H
CH
Tanaka
T
T
Ohga
S
S
Hara
T
T
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005312:Fetal Blood / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology*; D007378:Interleukins; D007694:Killer Cells, Natural / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D020382:Interleukin-18; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens