Case 11: Graft-Versus-Host Disease Flashcards
what is GVHD?
bone
marrow and most other sources of hematopoietic stem cells also contain mature
T lymphocytes, which may recognize the tissues of their new host as foreign and
cause a severe inflammatory disease in the recipient
what are the symptoms of GVHD?
rash
diarrhea
pneumonitis
liver damage
fibrosis
how do you make sure you have a successful BM transplant?
the immune system of the recipient must be destroyed and the
recipient rendered immunoincompetent
usually accomplished with lethal
doses of radiation or the injection of radiomimetic drugs such as busulfan, and the
use of immunosuppressive drugs
when does GVHD happen?
when there is a mismatch of classical MHC class I or class II molecules
Bone marrow is often depleted of T cells before transplantation, in an
attempt to avoid GVHD. However, in the treatment of leukemia by bone marrow
transplantation, T cells in the graft can have a beneficial effect. How do you explain
this?
The engrafted T cells seem to recognize allogeneic antigens on the recipient’s hematopoietic
cells and thus will attack the leukemic cells.
One such antigen, HB-1, which
is a B-cell lineage marker, is expressed by acute lymphoblastic leukemia cells, which
are B-lineage cells, and by B lymphocytes transformed by Epstein–Barr virus (EBV)
CD4 T cells in the graft that recognize foreign histocompatibility molecules
become activated and produce the cytokine interferon (IFN)-γ. This helps sustain
and increase GVHD. Why?
IFN-γ induces the expression of MHC molecules on cells; this makes GVHD worse,
because it provides more targets for the donor T cells.
John was given ATG (in addition to steroids) to control acute GVHD. Do you
know any other ways to achieve in vivo depletion of T lymphocytes?
In vivo T-cell depletion can also be achieved with the intravenous injection of monoclonal
antibodies, such as anti-CD3.
This approach is also used to treat initial graft
rejection in recipients of solid organ transplantation, but it is associated with a higher
risk of lymphoproliferative disease induced by the Epstein–Barr virus.
Monoclonal
antibodies targeting activated, but not resting, T lymphocytes have been also used
in the treatment of GVHD, and include anti-CD25 and anti-CD40L monoclonal
antibodies.
Why are the skin and intestinal tract the major sites of GVHD?
One reason could be that the skin and intestine express a higher level of MHC molecules
than other tissues.
The intestinal tract is also likely to be damaged by the preparative
cytotoxic treatments given to destroy the recipient’s bone marrow.
The damage
induces the production of cytokines; as well as inducing MHC molecules, these can
also drive GVHD and make the tissue susceptible to immunological attack.
