Mesenteric Lymph Node Tγδ Cells Induced by Gastrectomy in Mice Suppress Cell-Mediated Immune Response In Vitro via Released TGF-β

We have shown previously that gastrectomy, but not laparotomy alone, severely impairs contact sensitivity responses in vivo and selectively alters cell trafficking in gut associated lymphatic tissue. Here, we investigate the immunological role of different subpopulations of mesenteric lymph node cells (MLNCs) in the inhibition of contact sensitivity as well as their suppressive mechanisms. Suppressive cells were isolated from the mesenteric lymph nodes of gastrectomized mice and were added to cultures of lymphocytes from mice immunized with trinitrophenyl-chloride. These MLNCs inhibited the proliferation of sensitized lymphocytes in response to antigen. Depletion experiments revealed that the suppressive MLNCs are Tγδ+ cells, but not Tαβ+ cells. Neutralizing antibodies to IL-4, IL-10, and tissue growth factor-beta (TGF-β) revealed that suppression was dependent on TGF-β, but not the other cytokines. We conclude that surgical stress induced by gastrectomy causes accumulation of Tγδ+ lymphocytes in gut associated lymphatic tissue and that these cells suppress the cell-mediated response in vitro in an antigen-non specific manner via TGF-β. This cytokine can possibly prevent in vivo the development of autoimmune responses following severe tissue trauma in the gastrointestinal tract.

Key Words: gastrectomy, laparotomy, mesenteric lymphocytes, Tγδ cells, suppression, TGF-β