The in vivo mechanism of regulatory T cell (Treg cell) function in controlling autoimmunity remains controversial. Here we have used two-photon laser-scanning microscopy to analyze lymph node priming of diabetogenic T cells and to delineate the mechanisms of Treg cell control of autoimmunity in vivo. Islet antigen -specific CD4+CD25- T helper cells (TH cells) and Treg cells swarmed and arrested in the presence of autoantigens. These TH cell activities were progressively inhibited in the presence of increasing numbers of Treg cells. There were no detectable stable associations between Treg and TH cells during active suppression. In contrast, Treg cells directly interacted with dendritic cells bearing islet antigen. Such persistent Treg cell-dendritic cell contacts preceded the inhibition of TH cell activation by dendritic cells, supporting the idea that dendritic cells are central to Treg cell function in vivo.
Bibliographical noteFunding Information:
We thank S. Jiang, C. McArthur, C. Bennett, R.A. Hwang, F. Siedenberg, L. Braun, J. Belgum, S. Hayden, M. Sanderson and M. Bengttson for technical assistance, and members of the Bluestone laboratory for support. Supported by the Juvenile Diabetes Research Foundation (4-1999-841 and 32004232), National Insitutes of Health (R37 AI46643, P30 DK063720, R21 AI066097 and AI30663), Sandler–Howard Hughes Medical Institute Biomedical Research Support Program (5300246), Sandler New Technologies and the Canadian Institutes of Health Research and Alberta Heritage Foundation for Medical Research.