Basophils inhibit proliferation of CD 4 + T cells in autologous and allogeneic mixed lymphocyte reactions and limit disease activity in a murine model of graft versus host disease

• Published in: Immunology 2015-06, Vol.145 (2), p.202-212
• Main Authors: Hermann, Fabian J., Rodriguez Gomez, Manuel, Doser, Kristina, Edinger, Matthias, Hoffmann, Petra, Schiechl, Gabriela, Talke, Yvonne, Göbel, Nicole, Schmidbauer, Kathrin, Syed, Shahzad N., Brühl, Hilke, Mack, Matthias
• Format: Article
• Language: English
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12436

Basophils are known to modulate the phenotype of CD 4 + T cells and to enhance T helper type 2 responses in vitro and in vivo . In this study, we demonstrate that murine basophils inhibit proliferation of CD 4 + T cells in autologous and allogeneic mixed lymphocyte reactions. The inhibition is independent of F as and MHC class II , but dependent on activation of basophils with subsequent release of interleukin‐4 ( IL ‐4) and IL ‐6. The inhibitory effect of basophils on T ‐cell proliferation can be blocked with antibodies against IL ‐4 and IL ‐6 and is absent in IL ‐4/ IL ‐6 double‐deficient mice. In addition, we show that basophils and IL ‐4 have beneficial effects on disease activity in a murine model of acute graft‐versus‐host disease (Gv HD ). When basophils were depleted with the antibody MAR ‐1 before induction of Gv HD , weight loss, Gv HD score, mortality and plasma tumour necrosis factor levels were increased while injection of IL ‐4 improved Gv HD . Basophil‐depleted mice with Gv HD also have increased numbers of CD 4 + T cells in the mesenteric lymph nodes. Our data show for the first time that basophils suppress autologous and allogeneic CD 4 + T‐cell proliferation in an IL ‐4‐dependent manner.