Cellular and cytokine effectors of acute graft versus host disease

Graft Versus Host Diseases (GVHD) is a life threa-tening complication of allogeneic bone marrow trans-plantation (BMT), an important therapy for a number of hematologic diseases. In its acute phase, GVHD involves activation of proinflammatory cytokine cascades and immune effector cells that result in target tissue damage [1,2]. Multiple cellular populations and cytokines interact in a complex process that ultimately results in apoptotic injury in target organs (skin, gut, liver) and systemic disease. Shlomchik and colleagues have shown that host-derived antigen presenting cells (APCs) play a key role in the initiation of acute GVHD [3]. Advanced age of the BMT recipient is an important determinant of GVHD severity [4], and the increased risk of GVHD is one factor that often excludes older patients from consideration for allogeneic BMT. We have investigated the mechanisms by which advanced recipient age increases GVHD in murine BMT models of acute GVHD studies. 1. Results We evaluated the effect of recipient age in well-established murine models of GVHD elicited by both major and minor histocompatibility antigen differences between donors and recipients. Young (2 months), old (14-16 months) and very old (22 months) B6D2F1 (H-2b/d) mice were irradiated with 11 Gy TBI and trans-planted with BM and T cells as published [5]. We found that recipient age was a continuous variable with respect to GVHD severity. Severe GVHD developed in very old recipients with 100 % mortality by day 11. In old mice mortality was slightly but significantly delayed (P=0.03), and it was further delayed in young recipient