Differential effect of CTLA4Ig on murine graft-versus-host disease (GVHD) development: CTLA4Ig prevents both acute and chronic GVHD development but reverses only chronic GVHD.

摘要: The role of costimulation was examined in an vivo model alloantigen-driven Th1 or Th2 cytokine responses, the parent-into-F1 acute chronic graft-vs-host disease (GVHD), respectively. soluble fusion protein, murine CTLA4Ig, which blocks engagement CD28 by its natural ligand B7-1 and B7-2, administered either early, at time GVHD induction, delayed, after establishment effector responses (day 7). Early administration CTLA4Ig prevented development both preventing activation donor T cells, i.e., blocking characteristic production memory marker up-regulation on cells. Delayed unable to alter but did reverse as evidenced normalization serum autoantibody levels, normal host B cell numbers MHC class II expression, reduced expression CD40 ligand, CD4+ percentage cells not altered delayed CTLA4Ig. We conclude that this model, are equally susceptible costimulatory blockade onset disease; however, once mechanisms become established, only Th2-driven have a requirement for further continued expansion These data suggest humoral, lupus-like autoimmunity requires continuous help agents interrupt process may be beneficial.