Umbilical cord blood-naive T cells but not adult blood-naive T cells require HLA class II on antigen-presenting cells for allo-immune activation.
Because a relatively low incidence and severity of graft-versus-host disease after umbilical cord blood (UCB) transplantation is observed, we investigated whether T cells from UCB or adult blood (AB) were differentially activated by antigen-presenting cells with or without human leukocyte antigen (HLA)-DR expression. T cells from UCB or AB, or CD45RA(+) naive T cells and CD45RO(+) memory T cells separated from AB, were stimulated with the HLA-DR(+) or HLA-DR(-) cell line AML193. On days 1-3 after stimulation, numbers of interleukin (IL)-2, IL-4, IL-10 or interferon gamma (IFN-gamma)-secreting cells were determined by enzyme-linked immunospot analysis. No IL-4 or IL-10 was produced. AML193-DR(+) cells induced IL-2 and IFN-gamma secretion with slower kinetics and lower levels in UCB T cells than in AB T cells. AML193-DR(+) cells induced comparable IL-2 but higher IFN-gamma secretion in CD45RA(+) T cells from AB than in UCB T cells. AML193-DR(-) cells did not induce IL-2- or IFN-gamma secretion in UCB T cells, but stimulated both CD45RA(+) and CD45RO(+) T cells from AB to secrete IL-2 and IFN-gamma. Thus, not only the absence of memory T cells but also the inability to respond to HLA-DR-negative antigen-presenting cells and the slower kinetics and level of activation found for naive T cells from UCB as compared with AB may partly explain the reduced antirecipient reactivity after UCB transplantation.
Kloosterboer
F M
FM
Department of Hematology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. F.M.Kloosterboer@lumc.nl
van Luxemburg-Heijs
S A P
SA
Willemze
R
R
Falkenburg
J H F
JH
D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006680:HLA Antigens / Q000378:metabolism*; D015234:HLA-A Antigens / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D037181:Lectins, C-Type; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D006680:HLA Antigens; D015234:HLA-A Antigens; D006681:HLA-D Antigens; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D007376:Interleukin-2; D007519:Isoantigens; D037181:Lectins, C-Type; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens