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T lymphocyte activity is enhanced by costimulatory signals mediated through CD28 binding to B7-1/B7-2 on antigen-presenting cells. Several recent studies have shown that graft-versus-host disease (GVHD) can be inhibited by in vivo treatment with CTLA4Ig, which blocks CD28-B7 interactions. These findings prompted us to investigate the role of CD28 in acute GVHD, using gene-targeted mice. We performed the experiments in the context of strong allogeneic MHC stimulation (H2(b) anti-H2(d)) and weak stimulation (H2(d) anti-H2(b)). In both directions, efficient in vitro T-cell cytotoxicity and acute lethal GVHD were induced by CD28-deficient lymphocytes, which was only partially delayed when compared with wild-type mice. We conclude that lethal GVHD can develop without costimulation via CD28.

Type

Journal article

Journal

Transplantation

Publication Date

15/04/1997

Volume

63

Pages

1042 - 1044

Keywords

Abatacept, Acute Disease, Animals, Antigens, CD, Antigens, Differentiation, CD28 Antigens, CTLA-4 Antigen, Crosses, Genetic, Graft vs Host Disease, Immunoconjugates, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, T-Lymphocytes, Transplantation, Homologous