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Complete blockade of B7 family-mediated costimulation is necessary to
induce human alloantigen-specific anergy: a method to ameliorate graft-
versus-host disease and extend the donor pool
JG Gribben, EC Guinan, VA Boussiotis, XY Ke, L Linsley, C Sieff, GS Gray, GJ Freeman and LM Nadler
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston,
MA 02115, USA.
Graft-versus-host disease (GVHD) is initiated by adoptively transferred
donor T cells that recognize host alloantigens. Whereas the absence of
donor T-cell proliferation to host alloantigens in a mixed-leukocyte
reaction does not predict freedom from GVHD, the frequency of alloreactive
precursor helper T lymphocytes (pHTL) is predictive. Complete blockade of
87 family-mediated costimulation, but not of major histocompatibility
complex recognition or adhesion, induces host alloantigenic-specific energy
by reducing cytokine production below threshold levels necessary for common
gamma chain signaling. The associated reduction of alloreactive pHTL
frequency below that predictive for GVHD, without depletion of either
nonallospecific T cells or hematopoietic progenitors, has led us to embark
upon human clinical trials of haplomismatched allogeneic bone marrow
transplantation.
Volume 87,
Issue 11,
pp. 4887-4893,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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