Functional comparison of spleen dendritic cells and dendritic cells cultured in vitro from bone marrow precursors.
We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and present soluble antigen and stimulate major histocompatibility complex (MHC) Class II-restricted T cells. DC from spleen or BM cultures were equally able to stimulate the in vitro proliferation of allogeneic T cells or of antigen-specific T-cell receptor (TCR)-transgenic T cells. Both DC populations also induced comparable levels of IL-2 secretion by a T-cell hybridoma. Therefore, splenic and BM-derived DC express comparable levels of (Antigen + MHC Class II) ligands and/or costimulatory molecules and have comparable ability to stimulate T-cell responses. When presentation of a native protein antigen, rather than peptide, was evaluated, BM-derived DC were at least 50 times better than splenic DC at stimulating the proliferation of TCR-transgenic T cells. The antigen processing ability of the two populations was similar only when splenic DC were used immediately ex vivo. Therefore, unlike spleen DC, BM-derived DC maintain the capacity to process protein antigen for MHC Class II presentation during in vitro culture. Due to these characteristics, BM-derived DC may represent a useful tool in immunotherapy studies, as they combine high T-cell stimulatory properties with the capacity to process and present native antigen.
Malaghan Institute of Medical Research, Wellington South, New Zealand.
K
K
Garrigan
P
P
Moroni-Rawson
C
C
McMurray
I
I
Hermans
N
N
Abernethy
J
J
Watson
F
F
Ronchese
D000595:Amino Acid Sequence; D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor