Figure 1. Molecular Basis of Costirnulation for IL-2 Production APC, antigen-presenting cell; IL-2, interleukin-2; PLCy1, phospholipase C-y1; PIP2, phosphatidylinositol bisphosphate; IP3, inositol 1, 4, 5-trisphosphate; DAG, diacylglycerol; PKC, protein kinase C; NF-ATc, cytoplasmic component of nuclear factor of activated T cells.

In the presence of costimulation, anergy induction is prevented (Harding et al., 1992). This appears to be a consequence of the cell division following IL-2 production, which is thought to dilute any inhibitor (s) that forms (Jenkins, 1992). In model systems anergy can be reversed by addition of IL-2 even after its full induction, although four or more division cycles are required for complete reversal. Thus, the total amount of IL-2 produced in an immune response, which is heavily dependent on costimulation, plays a critical role in determining the extent to which anergy is induced.