Dendritic cells rapidly undergo apoptosis in vitro following culture with activated CD4+ Valpha24 natural killer T cells expressing CD40L.
Human Valpha24 natural killer T (Valpha24NKT) cells are activated by alpha-glycosylceramide-pulsed dendritic cells (DCs) in a CD1d-dependent and T-cell receptor-mediated manner. There are two major subpopulations of Valpha24NKT cells, CD4- CD8- Valpha24NKT and CD4+ Valpha24NKT cells. We have recently shown that activated CD4- CD8- Valpha24NKT cells have cytotoxic activity against DCs, but knowledge of the molecules responsible for cytotoxicity of Valpha24NKT cells is currently limited. We aimed to investigate whether CD4+ Valpha24NKT cells also have cytotoxic activity against DCs and to determine the mechanisms underlying any observed cytotoxic activity. We demonstrated that activated CD4+ Valpha24NKT cells [CD40 ligand (CD40L) -positive] have cytotoxic activity against DCs (strongly CD40-positive), but not against monocytes (weakly CD40-positive) or phytohaemagglutinin blast T cells (CD40-negative), and that apoptosis of DCs significantly contributes to the observed cytotoxicity. The apoptosis of DCs following culture with activated CD4+ Valpha24NKT cells, but not with resting CD4+ Valpha24NKT cells (CD40L-negative), was partially inhibited by anti-CD40L mAb. Direct ligation of CD40 on the DCs by the anti-CD40 antibody also induced apoptosis of DCs. Our results suggest that CD40-CD40L interaction plays an important role in the induction of apoptosis of DCs following culture with activated CD4+ Valpha24NKT cells. The apoptosis of DCs from normal donors, triggered by the CD40-CD40L interaction, may contribute to the homeostatic regulation of the normal human immune system, preventing the interminable activation of activated CD4+ Valpha24NKT cells by virtue of apoptosis of DCs.
Department of Research, The Japanese Red Cross Central Blood Centre, Tokyo, Japan.
M
M
Nieda
A
A
Kikuchi
A
A
nicol
Y
Y
Koezuka
Y
Y
Ando
S
S
Ishihara
N
N
Lapteva
T
T
Yabe
K
K
Tokunaga
K
K
Tadokoro
T
T
Juji
D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis
D000911:Antibodies, Monoclonal; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand