Basophils inhibit proliferation of CD4+ T cells in autologous and allogeneic mixed lymphocyte reactions and limit disease activity in a murine model of graft versus host disease.

Basophils are known to modulate the phenotype of CD4⁺ 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 CD4⁺ T cells in autologous and allogeneic mixed lymphocyte reactions. The inhibition is independent of Fas 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 CD4⁺ T cells in the mesenteric lymph nodes. Our data show for the first time that basophils suppress autologous and allogeneic CD4⁺ T-cell proliferation in an IL-4-dependent manner. [ABSTRACT FROM AUTHOR]