Blood, 15 December 2002, Vol. 100, No. 13, pp. 4255-4255
A major minor for GVHD
Acute graft-versus-host disease (GVHD) after allogeneic
bone marrow transplantation (BMT) is a complex process that involves donor T cells and multiple cellular and cytokine effectors. Detailed knowledge of T-cell responses to minor histocompatibility (H) antigens
is scant. In this issue Choi and colleagues (page 4259) used mouse
models of GVHD to multiple minor H antigens in order to track donor T
cells through several GVHD target organs (spleen, liver, lung) in real
time and completed this picture in several important ways. First, they
demonstrate that nearly a quarter of the donor cells respond to
a single minor antigen, H60. This response occurred in several
donor/recipient strain combinations, suggesting that strong
immunodominance will be broadly applicable; additional matches at a
handful of "major" minors may therefore significantly reduce the
risk of GVHD between HLA-identical donors and recipients. Second, the
donor T cells expanded simultaneously in the liver, lung, and spleen,
suggesting that donor T cells interact directly with
antigen-presenting cells of the host not only in secondary lymphoid
tissue but in target organs as well. Third, clonal T-cell expansion
occurred early and contracted back to baseline by day 14, before the
onset of GVHD mortality. Three weeks after transplantation, target
organs are infiltrated by cells of the myeloid lineage, suggesting an
important role for non-T cells as GVHD effectors. Although the
conclusions of all animal models must be extrapolated to the clinical
setting with caution, such real time, detailed analysis sheds
significant light on important aspects of GVHD pathophysiology that
have heretofore remained murky.
James Ferrara
University of
Michigan
