[Increase of regulatory T cells in the lymph node of cathepsin L mutant mice].

Regulatory CD4+CD25+Foxp3+ T cells (Treg) have been implicated in different pathologies including cancer, infections and autoimmune diseases and in the rejection of allogeneic organ transplantation. Thus, modulation of Treg activity has a great potential in the treatment of these pathologies. Herein, we evaluated the influence of cathepsin L (CTSL) on Treg homeostasis. CTSL mutant mice (CTSLnkt/nkt) showed a decrease in the absolute number of thymic Treg cells. In contrast, the absolute number of lymph node Treg cells and their frequency within CD4+ cells were increased. The absence of CTSL activity in CD4+ T cells -and not in their environment- increased the proliferation rate of lymph node CD4+ T cells. Treg and T CD4+ conventional (CD4+CD25-Foxp3-) cells from mutant mice showed similar increases in their proliferative levels as compared with control mice, suggesting that although proliferation contributes to the increases in their number, the augmentation in the frequency of Treg cells is not only associated to increases in proliferation. Furthermore, the Treg apoptosis rate was not decreased in the lymph node of CTSLnkt/nkt mice. Taking into account that the daily CD4+ thymic production is diminished in mutant mice, our results suggest that peripheral Treg increases are probably not the result of increased thymic output and raise the possibility that a conversion to Treg phenotype would be favored in the CD4+ T cells peripheral pool of CTSL mutant mice.