TNF enhances CD4+ T cell alloproliferation, IFN-gamma responses, and intestinal graft-versus-host disease by IL-12-independent mechanisms.

TNF Enhances CD4 T Cell Alloproliferation, IFN- Responses, and Intestinal Graft-Versus-Host Disease by IL-12-Independent Mechanisms

IL-12-independent LIGHT signaling enhances MHC class II disparate CD4+ T cell alloproliferation, IFN-gamma responses, and intestinal graft-versus-host disease.

Inhibition of LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)/herpes simplex virus entry mediator (HVEM) and LIGHT/lymphotoxin beta receptor (LT beta R) interactions decreases mortality in MHC class I and II disparate graft-vs-host disease (GVHD). The present studies assessed the effects of these interactions on the generation of CD4+ T cell alloresponses in M...

Interleukin-12 inhibits murine graft-versus-host disease.

Interleukin-12 (IL-12) is a potent immunostimulatory cytokine and an inducer of type-1 T-helper cell activity and of cytotoxic T lymphocyte and natural killer cell function. We report here the paradoxical observation that a single injection of 4,900 IU of recombinant murine IL-12 inhibits acute graft-versus-host disease (GVHD) in a fully major histocompatibility complex (MHC) plus multiple mino...

Interleukin-12 preserves the graft-versus-leukemia effect of allogeneic CD8 T cells while inhibiting CD4-dependent graft-versus-host disease in mice.

We have recently demonstrated that a single injection of 4,900 IU of interleukin-12 (IL-12) on the day of bone marrow transplantation (BMT) markedly inhibits acute graft-versus-host disease (GVHD) in a fully major histocompatibility complex plus minor antigen-mismatched BMT model (A/J --> B10, H-2(a) --> H-2(b)), in which donor CD4(+) T cells are required for the induction of acute GVHD. We sho...

CD40 engagement enhances antigen-presenting langerhans cell priming of IFN-gamma-producing CD4+ and CD8+ T cells independently of IL-12.

The delivery of CD40 signaling to APCs during T cell priming enhances many T cell-mediated immune responses. Although CD40 signaling up-regulates APC production of IL-12, the impact of this increased production on T cell priming is unclear. In this study an IL-12-independent T cell-mediated immune response, contact hypersensitivity (CHS), was used to further investigate the effect of CD40 ligat...