Graft-versus-host disease (GVHD) is

an example of apoptosis which occurs

in allogeneic hematopoietic stem cell
transplant recipients. The transplanted
marrow has cytotoxic T-cells which
recognize the new host proteins (usually
HLA) as foreign. Organs typically involved
include the skin, mucosa, liver, and GI
tract. The histologic hallmark of GVHD is
apoptosis.

Robin’s 9th ed - 139 pg:

Graft-Versus-Host Disease (GVHD). This occurs when

immunologically competent T cells (or their precursors) are
transplanted into recipients who are immunologically
compromised. Although GVHD happens most commonly
in the setting of allogeneic HSC transplantation (usually
involving minor histocompatibility mismatches between
donor and recipient), it also may occur after transplantation of solid organs rich in lymphoid cells (e.g., the liver)
or after transfusion of nonirradiated blood. On receiving
allogeneic HSCs, an immunologically compromised host
cannot reject the graft, but T cells present in the donor graft
perceive the recipient’s tissue as “foreign” and react against
it. This results in the activation of both CD4+ and CD8+ T
cells, ultimately causing inflammation and killing host
cells.
• Acute GVHD (occurring days to weeks after transplantation) causes epithelial cell necrosis in three principal
target organs: liver, skin, and gut. Destruction of small
bile ducts gives rise to jaundice, and mucosal ulceration
of the gut results in bloody diarrhea. Cutaneous involvement is manifested by a generalized rash.
• Chronic GVHD may follow the acute syndrome or may
occur insidiously. The patients develop skin lesions
resembling those of SS (discussed earlier) and manifestations mimicking other autoimmune disorders.
GVHD is a potentially lethal complication that can be
minimized but not eliminated by HLA matching. As
another potential solution, donor T cells can be depleted
before marrow transplant. This protocol has proved to be
a mixed blessing: The risk of GVHD is reduced, but the
incidence of graft failure and (in those with the disease) the

recurrence of leukemia increase. It seems that the multifunctional T cells not only mediate GVHD but also are
required for the effcient engraftment of the transplanted
HSCs and elimination of leukemia cells (so-called graftversus-leukemia effect).
Immune Defciencies. These are often of prolonged duration in recipients of HSC transplants. Among the many
reasons for this impairment is the slow reconstitution of
the recipient’s adaptive immune system, which is destroyed
or suppressed to allow the graft to take and requires many
months to recover. During this vulnerable period, recipients are susceptible to a variety of infections, mostly viral,
such as cytomegalovirus (CMV) and EBV infections