CD28 and graft versus host disease: Blockade of CD28 co-stimulatory domain with specific CTLA-4Ig inhibitor may also be effective in preventing GVHD; T cell activation requires at least two signals: the first is triggered by antigen-specific TCR engagement of antigen-MHC and the second is provided by CD28 binding to B7 ligands (CD80 or CD86) so engaging APC; T cells receiving the first but not second co-stimulatory signal, acquire antigen-specific anergy.