Acute graft-versus-host disease without costimulation via CD28.

Journal article

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.

Authors: Speiser, D; Bachmann, M; Shahinian, A; Mak, T; Ohashi, P

• Publication status: Published
• Journal: Transplantation
• Volume: 63
• Issue: 7
• Pages: 1042-1044
• Publication date: 1997-04-01
• DOI: 10.1097/00007890-199704150-00028
• EISSN: 1534-6080
• ISSN: 0041-1337
• Language: English
• Keywords: Animals; Mice, Inbred BALB C; Mice; CTLA-4 Antigen; Antigens, CD; Mice, Inbred C57BL; Crosses, Genetic; Antigens, Differentiation; Transplantation, Homologous; T-Lymphocytes; Acute Disease; Immunoconjugates; Lymphocyte Activation; Antigens, CD28; Graft vs Host Disease