Divergent roles of dendritic cells in the induction and maintenance of T cell tolerance in different secondary lymphoid organs

Dendritic cells (DCs) have the capacity to initiate immune responses. Some studies postulated that in the absence of costimulation, DCs induce abortive antigen-specific T cell activation followed by T-cell deletion or unresponsiveness. To examine the peripheral conditions of antigen presentation that could lead to T cell tolerance when DCs are the exclusive APCs, we took advantage of the 2aT transgenic model. In this model, transgenic T cells (2aT cells) recognize a portion of the IgG2ab, the Bpep, in association with the MHC molecule, I-Ad. We have generated a transgenic mouse model (DC-Tg) in which the I-Ad β chain is covalently linked to the Bpep and is expressed under the control of CD11c promoter. We obtained two different groups of founders showing high or low levels of Bpep presentation (DC-Tghigh and DC-Tglow). 105 2aT cells were adoptively transferred into both groups of mice and their fate was followed. After the injection, 2aT cells underwent a robust clonal expansion and IFNg serum levels increased. Then, the primary response was controlled and 2aT cells had different fate in the two groups of recipients: in DC-Tghigh mice, they rapidly downregulated the T cell receptor (TCR); alterenatively, part of the 2aT cells transferred into DC-Tglow mice differentiated into Tregs able to suppress the T cell response. Both these phenomena occurred in the lymph nodes, while the spleens appeared not to be sites of tolerization.