Efficient priming of antigen-specific cytotoxic T lymphocytes by human cord blood dendritic cells

被引:37
作者
Salio, M [1 ]
Dulphy, N
Renneson, J
Herbert, M
McMichael, A
Marchant, A
Cerundolo, V
机构
[1] John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Tumour Immunol Unit, Oxford OX3 9DS, England
[2] John Radcliffe Hosp, Weatherall Inst Mol Med, Human Immunol Unit, Oxford OX3 9DS, England
关键词
neonatal immunity; T cell polarization; tetramer;
D O I
10.1093/intimm/dxg123
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Previous studies have suggested that defective immune responses in early life may be related to the immaturity of neonatal antigen-presenting cells. To test this hypothesis, we assessed the capacity of neonatal dendritic cells (DC) to prime and polarize in vitro human naive antigen-specific T cells. We report that mature cord blood DC efficiently prime an oligoclonal population of antigen-specific CD8 T cells, capable of cytolytic activity and IFN-gamma secretion. In contrast, cells primed by immature cord blood DC do not acquire cytolytic activity and secrete lower amounts of IFN-gamma. Upon priming by either immature or mature DC, neonatal T cells acquire markers of activation and differentiation towards effector-memory cells. Our results demonstrate that, if appropriately activated, neonatal DC can prime efficient cytotoxic T lymphocyte (CTL) responses. Furthermore, these findings have important implications for the development of vaccine strategies in early life and for the reconstitution of a functional CTL repertoire after bone marrow transplantation.
引用
收藏
页码:1265 / 1273
页数:9
相关论文
共 52 条
[1]   T-cell function in newborn mice and humans [J].
Adkins, B .
IMMUNOLOGY TODAY, 1999, 20 (07) :330-335
[2]   Phenotypic analysis of antigen-specific T lymphocytes [J].
Altman, JD ;
Moss, PAH ;
Goulder, PJR ;
Barouch, DH ;
McHeyzerWilliams, MG ;
Bell, JI ;
McMichael, AJ ;
Davis, MM .
SCIENCE, 1996, 274 (5284) :94-96
[3]   Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections [J].
Appay, V ;
Dunbar, PR ;
Callan, M ;
Klenerman, P ;
Gillespie, GMA ;
Papagno, L ;
Ogg, GS ;
King, A ;
Lechner, F ;
Spina, CA ;
Little, S ;
Havlir, DV ;
Richman, DD ;
Gruener, N ;
Pape, G ;
Waters, A ;
Easterbrook, P ;
Salio, M ;
Cerundolo, V ;
McMichael, AJ ;
Rowland-Jones, SL .
NATURE MEDICINE, 2002, 8 (04) :379-385
[4]   HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function [J].
Appay, V ;
Nixon, DF ;
Donahoe, SM ;
Gillespie, GMA ;
Dong, T ;
King, A ;
Ogg, GS ;
Spiegel, HML ;
Conlon, C ;
Spina, CA ;
Havlir, DV ;
Richman, DD ;
Waters, A ;
Easterbrook, P ;
McMichael, AJ ;
Rowland-Jones, SL .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :63-75
[5]   Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells [J].
Arpinati, M ;
Green, CL ;
Heimfeld, S ;
Heuser, JE ;
Anasetti, C .
BLOOD, 2000, 95 (08) :2484-2490
[6]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[7]   Dendritic cells can be successfully generated from CD34+ cord blood cells in the presence of autologous cord blood plasma [J].
Borràs, FE ;
Matthews, NC ;
Patel, R ;
Navarrete, C .
BONE MARROW TRANSPLANTATION, 2000, 26 (04) :371-376
[8]   Interleukin-3 and interferon β cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties [J].
Buelens, C ;
Bartholomé, EJ ;
Amraoui, Z ;
Boutriaux, M ;
Salmon, I ;
Thielemans, K ;
Willems, F ;
Goldman, M .
BLOOD, 2002, 99 (03) :993-998
[9]   Immune responses of infants to infection with respiratory viruses and live attenuated respiratory virus candidate vaccines [J].
Crowe, JE .
VACCINE, 1998, 16 (14-15) :1423-1432
[10]   Efficient in vivo priming of specific cytotoxic T cell responses by neonatal dendritic cells [J].
Dadaglio, G ;
Sun, CM ;
Lo-Man, R ;
Siegrist, CA ;
Leclerc, C .
JOURNAL OF IMMUNOLOGY, 2002, 168 (05) :2219-2224