Biology Reference
In-Depth Information
ch
14
B and T cells in chronic
graft-versus-host disease
and graft-versus-leukemia
Caron A Jacobson, Jerome Ritz
Division of Hematologic Malignancies, Dana-Farber Cancer Institute,
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
299
Key points
•
Chronicgraft-versus-hostdisease(cGVHD)isprimarilytheresultofafailureto
achieveT-celltolerancefollowingtransplantation.
•
TheinabilitytoestablishormaintainT-celltoleranceresultsinthepersistenceof
alloreactiveconventionalCD4andCD8Tcells,survivalofauto-andalloreac-
tiveBcells,andpersistenceofcytokineprofilesthatpromoteinflammationand
fibrosisoftargettissues.
•
Graft-versus-leukemia/graft-versus-tumor
(GVL/GVT) effects are mediated
in part by a failure to achieve tolerance (and thus correlatewith cGVHD) but
arealsomediatedbyaspecificanti-tumor immuneresponsedirectedagainst
tumor-specificantigens.
•
Strategies to improve the efficacy and safety of transplantation involve better
treatmentsforcGVHD,enhancementofspecificanti-tumorGVL/GVT,andsep-
arationofGVHDfromGVL/GVT.
Introduction
Chronic graft-versus-host disease (cGVHD) is a significant complication fol-
lowing allogeneic stem cell transplantation (ASCT), occurring in 25-65% of
patients
[1]
. It is a pleiomorphic disease with manifestations that resemble
those seen in a variety of autoimmune diseases, including systemic lupus
erythematosus (SLE), Sjogren's syndrome, and systemic sclerosis
[2,3]
. It
can involve the lungs, liver, salivary and lacrimal glands, skin, eyes, and gas-
trointestinal tract, and injury to these tissues causes significant long-term
morbidity and mortality for patients following ASCT
[4]
. Mortality related to
cGVHD has been reported to be as high as 30%
[5]
. Our understanding of
the immune pathogenesis of the disease, however, is limited owing in part to
the fact that few animal models have been developed that accurately mimic
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