Antigen dose, type of antigen-presenting cell and time of differentiation contribute to the T helper 1/T helper 2 polarization of naive T cells.
Antigenic encounter by T cells induces immunological synapse formation and T-cell activation. Using different concentrations of toxic shock syndrome toxin-1 (TSST-1) as stimulus, we examined the capacities of dendritic cells (DC) and macrophages (Mphi) to prime syngeneic naive T cells. DCs were, under all experimental settings, more efficient than Mphi at clustering T cells. Translocation of the T-cell receptor (TCR) to the contact area was found to be induced by DCs, as well as by Mphi, in an antigen-dependent manner, although Mphi were less efficient at inducing TCR translocation. Capping of protein kinase C theta (PKCtheta) was also antigen dependent but induced exclusively by DCs. Likewise, DCs were found to be more potent inducers of interleukin-2 (IL-2) production and proliferation of naive T cells than Mphi. After 3 days of culture, DCs presenting 100 ng/ml TSST-1 induced interferon-gamma (IFN-gamma)-secreting cells, whereas Mphi did not. After 7 days of culture, DCs presenting 0.1 ng/ml TSST-1, and Mphi presenting high (as well as low) doses of TSST-1, induced IL-4-producing cells. We therefore provide evidence to show that antigen dose, type of antigen-presenting cell and time of differentiation can contribute to T-cell differentiation.
Rothoeft
T
T
Children's Hospital of the Ruhr-University Bochum, Bochum, Germany. Tobias.Rothoeft@ruhr-uni-bochum.de
Gonschorek
A
A
Bartz
H
H
Anhenn
O
O
Schauer
U
U
D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001427:Bacterial Toxins; D002454:Cell Differentiation; D002455:Cell Division; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004768:Enterotoxins / Q000008:administration & dosage* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D011493:Protein Kinase C / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018089:Superantigens; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
D015703:Antigens, CD; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D011493:Protein Kinase C