The ratio between dendritic cells and T cells determines the outcome of their encounter: proliferation versus deletion.
Dendritic cells (DC) either induce T cell tolerance or contribute to the initiation and modulation of T and B cell responses. Since many of the variables determining the thresholds of naive T cell priming were defined in vitro using a homogeneously matured DC population, we here focused on partially mature DC which might reflect the occurrence of tumor-infiltrating and thymic DC. To predict how those DC regulate the induction of antigen-specific T cell proliferation and T cell tolerance, we co-cultured ovalbumin-pulsed murine DC at different ratios with antigen-specific DO11.10 transgenic T cells. Whereas partially mature DC at a DC/T cell ratio of 1:10 supported proliferation, a DC/T cell ratio of 1:2 induced proliferation arrest in naive CD4+ T cells. The acquisition of the NK cell inhibitory markers NK1.1 and KLRG on T cells exposed to high numbers of DC suggests a role for these molecules in the protection of antigen-responsive T cells from exhaustion by overstimulation. Mechanistically, abortive T cell proliferation upon encounter of high numbers of partially mature DC is caused by an apoptosis-related pathway, suggesting that excessive antigen density without sufficient costimulation results in activation-induced cell death.
Höpken
Uta E
UE
Max-Delbrück-Center for Molecular Medicine, Department of Tumorgenetics and Immunogenetics, Berlin, Germany.
Lehmann
Insa
I
Droese
Jana
J
Lipp
Martin
M
Schüler
Thomas
T
Rehm
Armin
A
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic