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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2858-2866
IMMUNOBIOLOGY
Myeloid blood CD11c+ dendritic cells and
monocyte-derived dendritic cells differ in their ability to stimulate
T lymphocytes
Yuko Osugi,
Slavica Vuckovic, and
Derek N. J. Hart
From the Department of Developmental Medicine
(Pediatrics), D-5, Osaka University Graduate School of Medicine, Japan;
and the Mater Medical Research Institute, South Brisbane, Queensland,
Australia.
Dendritic cells (DCs) initiate and direct immune responses. Recent
studies have defined different DC populations, therefore we undertook
this study comparing 2 types of myeloid DCs: blood CD11c+
DCs and in vitro monocyte-derived DCs (Mo-DCs), which are both candidates as cellular adjuvants for cancer immunotherapy. Blood CD11c+ DCs were prepared by cell sorting from peripheral
blood mononuclear cells cultured overnight in RPMI 1640 medium
supplemented with autologous or pooled AB serum. Mo-DCs were prepared
in the same medium using granulocyte macrophage-colony-stimulating
factor (GM-CSF)/interleukin 4 (IL-4) and differentiated/activated with lipopolysaccharide or monocyte-conditioned medium (ActMo-DCs). Morphologically, differences between the DC preparations were noted
both at a light and and electron microscopic level. Blood CD11c+ DCs expressed similar levels of HLA-DR, CD40, CD86,
and CD83 as Mo-DCs. CD209 was present on Mo-DCs but not on blood
CD11c+ DCs. Blood CD11c+ DCs generated a lower
proliferative mixed leukocyte response (MLR) than Mo-DCs. Blood
CD11c+ DCs loaded with 0.1 µg/mL tetanus toxoid
(TT)-generated greater T lymphocyte proliferative responses than did
Mo-DCs or ActMo-DCs, but when loaded with higher TT concentrations no
difference in T lymphocyte proliferative response was observed. Keyhole
limpet hemocyanin (KLH)-loaded blood CD11c+ DCs generated
greater T lymphocyte proliferative responses than Mo-DCs or ActMo-DCs.
Allogeneic MLR- or KLH-specific responses induced by blood
CD11c+ DCs generated more Th1 effectors than the responses
induced by Mo-DCs or ActMo-DCs. These data establish several
differences in the properties of blood CD11c+ DCs, Mo-DCs,
and ActMo-DCs, which suggest that blood DCs merit further consideration
as DC preparations for clinical programs are evolved.
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