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
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 hel...
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Published in | Blood Vol. 87; no. 11; pp. 4887 - 4893 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
Elsevier Inc
01.06.1996
The Americain Society of Hematology |
Subjects | |
Online Access | Get full text |
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Summary: | 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 B7 family-mediated costimulation, but not of major histocompatibility complex recognition or adhesion, induces host alloantigen-specific anergy by reducing cytokine production below threshold levels necessary for common γ-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. |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood.V87.11.4887.bloodjournal87114887 |