Polarized type 2 alloreactive CD4+ and CD8+ donor T cells fail to induce experimental acute graft-versus-host disease.

W Krenger, KM Snyder, JC Byon… - … (Baltimore, Md.: 1950 …, 1995 - journals.aai.org
W Krenger, KM Snyder, JC Byon, G Falzarano, JL Ferrara
Journal of Immunology (Baltimore, Md.: 1950), 1995journals.aai.org
Acute graft-vs-host disease (GVHD) is thought to be mediated by alloreactive T cells with a
type 1 cytokine phenotype. To prevent the development of acute GVHD, we have
successfully polarized mature donor T cells toward a type 2 cytokine phenotype ex-vivo by
incubating them with murine rIL-4 in a primary MLC. Polarized type 2 T cells were then
transplanted with T cell-depleted bone marrow cells into irradiated recipients across either
MHC class II (bm12--> C57BL/6) or class I (bm1--> C57BL/6) barriers, and the intensity of …
Abstract
Acute graft-vs-host disease (GVHD) is thought to be mediated by alloreactive T cells with a type 1 cytokine phenotype. To prevent the development of acute GVHD, we have successfully polarized mature donor T cells toward a type 2 cytokine phenotype ex-vivo by incubating them with murine rIL-4 in a primary MLC. Polarized type 2 T cells were then transplanted with T cell-depleted bone marrow cells into irradiated recipients across either MHC class II (bm12-->C57BL/6) or class I (bm1-->C57BL/6) barriers, and the intensity of GVHD was measured by assessment of several in vitro and in vivo parameters. The injection of polarized type 2 T cells abrogated the mitogen-induced production of IFN-gamma by splenocytes from transplanted hosts on day 13 after bone marrow transplantation (BMT). Injection of polarized type 2 T cells failed to induce secretion of the effector phase cytokine TNF-alpha by splenocytes stimulated with LPS both in vitro and in vivo, and survival of transplanted mice after i.v. injection with LPS was significantly improved. Furthermore, cell-mixing experiments revealed that polarized type 2 T cells were able to inhibit type 1 cytokine responses induced by naive T cells after BMT. These data demonstrate that both polarized CD4+ and CD8+ type 2 alloreactive donor T cells can be generated in vitro from mature T cell populations. These cells function in vivo to inhibit type 1 T cell responses, and such inhibition attenuates the systemic morbidity of GVHD after BMT across both MHC class II or class I barriers in mice.
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