Treg cells modulate chemokines and cytokines in lymph node stromal cells

The LN is composed of stromal cells that form a conduit system and provide a structural environment for homeostasis and differentiation of lymphocytes. We aim to characterize the effect of stromal cells to attract and instruct DC and T cells to initiate immune responses. In our skin transplantation model, Tregs are able to delay the rejection of the allograft in a cell number dependent manner. We isolated stroma cells from LN of mice rejecting (Teff) or tolerating the graft (Teff:Treg). Only in the Teff group, we found lower numbers of TRCs (gp38+CD31-) and higher numbers of double negative cells (gp38-CD31-). Furthermore, TRC from the Teff group down-regulated the production of the chemoattractants CCL19 and CCL21, and different cytokines including IL-7 and FLT3L. The presence of Tregs inhibited the down-regulation or maintained the expression of analyzed molecules. We found that IL-7 increases the suppressive capacity of Tregs in response to alloantigens in vitro. The induction of NOS3 is enhanced in TRCs during graft rejection, which is probably a response to IFNg release in the Teff but not Teff:Treg group. Taken together our results indicate that Tregs influences the expression pattern of stroma cells by inhibiting effector T cells functions in the LN.