Antigen-specific T lymphocytes were injected into mLN-bearing and mLN-resected mice. Afterwards the mice were treated with ovalbumin and retinoic acid by subcutaneous injection, and the up-regulation of gut-specific homing molecules on these T lymphocytes was measured within peripheral LN, Ibrutinib research buy as well as the gut. It was shown that after treatment with ovalbumin and retinoic acid at the peripheral site, effector cells were generated which home to the gut region independent of the presence of the mLN [45]. Other groups working on graft-versus-host disease (GvHD), which is a major problem after transplantation, removed LN to analyse the survival of the graft as well

as the host. Lück et al. studied extensively the effect of mLN resection after small bowel transplantation in the dependence of major histocompatibility complex (MHC) expression. After removing the mLN the animals survived transplantation, whereas mLN-bearing rats died within 2 weeks. Furthermore, MHC molecules were found to play a major role in GvHD and the mLN were also involved in this process by sending lymphocytes to the small bowel graft [46–48]. However, the dependence of graft survival and LN were also analysed by other groups. They all concluded that the regional LN of the graft are responsible for the

GvHD, independent of the location of the transplantation [49–51]. Recently, Panoskaltsis-Mortari et al., using the ROCK inhibitor bone marrow transplantation (BMT) model, showed accumulation and proliferation of T cells in the LN and spleen [52]. Further studies identified cell surface molecules such

as CD103, leucocyte function-associated antigen-1 (LFA-1) or L-selectin and β7 integrin on T lymphocytes, which enables them to migrate in a molecule-dependent manner to the target organs [9,53,54]. In all these studies the absence of the molecules increased the animals’ Cyclic nucleotide phosphodiesterase survival. Furthermore, DC, which imprinted lymphocytes, were identified as playing a major role in GvHD [55]. Thus, removing the mLN not only allowed the identification of various specific cells coming from the draining area, but also showed the impact on immune responses triggered in the LN. A further function of LN is the induction of mucosal tolerance. Oral tolerance is the unresponsiveness of the immune system on recognizing a harmless antigen. This phenomenon has hardly been studied and is little understood. The presence of DC and also regulatory T cells (Tregs) coming from the draining area seem to be essential for the induction of tolerance after feeding low doses of antigen [56–58]. Recently, it became clear that CD103+ DC which migrate permanently from the lamina propria to the mLN, carrying in the majority of cases microbial antigens from the commensal bacteria, produce IL-10, transforming growth factor (TGF)-β, retinoic acid and indoleamine-2, 3-dioxygenase (IDO) [57,59–62].