The Yin and Yang of T Cell Costimulation

The Perspective by J. Allison and M. Krummel discusses a paper in this issue of Science by Waterhouse et al . ( p. 985 ), which reports the lymphoproliferative phenotype of mice lacking the T cell antigen CTLA-4. The function of this molecule has been elusive, but the pronounced lymphadenopathy of these knockout mice provides strong evidence that it works in opposition to the positive signal generated by the costimulatory T cell antigen receptor-peptide and CD28-B7 interactions.