FIG. 1.

The normal immune response is outlined in the upper portion of the figure, with the naive T cell receiving the proper antigen-MHC type II signal and proper costimulation, leading to production of an activated T cell producing enough IL-2 to develop and clonally expand toward a Th1 or Th2 type under the influence of IL-12/INF-γ or IL-4, respectively. Under conditions of inadequate B7 costimulation or altered peptide ligand-TCR binding, insufficient IL-2 is generated to sustain T-cell proliferation and either no response, T-cell death, or T-cell anergy is the possible outcome. Inadequate B7 costimulation may also lead to preferential binding to CTLA-4 over CD28 on the naive T cell, also leading to T-cell anergy.