Graft-versus-host disease causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Overview[edit | edit source]

The major cause of GvHD is HLA disparity between the recipient and host, resulting in abnormal immune activation against the recipient. This concept was proposed by Billingham in the 1960s.

Causes[edit | edit source]

According to the Billingham Criteria, 3 criteria must be met in order for GvHD to occur.^[1]

• Administration of an immunocompetent graft, with viable and functional immune cells.
• The recipient is immunologically disperate and histoincompatible.
• The recipient is immunocompromised and therefore cannot destroy or inactivate the transplanted cells.

After bone marrow transplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissues of the transplant recipient after perceiving host tissues as antigenically foreign. The T cells produce an excess of cytokines, including TNF alpha and interferon-gamma (IFNg). A wide range of host antigens can initiate graft-versus-host-disease, among them the human leukocyte antigens (HLAs). However, graft-versus-host disease can occur even when HLA-identical siblings are the donors. HLA-identical siblings or HLA-identical unrelated donors often have genetically different proteins (called minor histocompatibility antigens) that can be presented by MHC molecules to the recipient's T cells, which see these antigens as foreign and so mount an immune response.

While donor T cells are undesirable as effector cells of GvHD, they are valuable for engraftment by preventing the recipient's residual immune system from rejecting the bone marrow graft (host-versus-graft). Additionally, as bone marrow transplantation is frequently used to treat cancer, mainly leukemias, donor T cells have proven to have a valuable graft-versus-tumor effect. A great deal of current research on allogeneic bone marrow transplantation involves attempts to separate the undesirable graft-vs-host-disease aspects of T cell physiology from the desirable graft-versus-tumor effect.

References[edit | edit source]

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