The study investigates the induction of peripheral T cell tolerance in vivo and finds that it requires costimulation by B7 molecules. Specifically, blocking B7 molecules prevents the induction of anergy, maintaining T cells in a functionally competent state. The induction of anergy is further prevented by blocking CTLA-4, an inhibitory receptor that recognizes B7 molecules. This suggests that T cell tolerance is not due to a lack of costimulation but rather to specific recognition of B7 molecules by CTLA-4. In contrast, blocking CD28 on T cells prevents priming but does not affect the induction of tolerance. The results indicate that the outcome of antigen recognition by T cells is determined by the interaction between CD28 or CTLA-4 on T cells and B7 molecules on antigen-presenting cells (APCs). The findings have implications for understanding the mechanisms of T cell anergy and the regulation of immune responses.The study investigates the induction of peripheral T cell tolerance in vivo and finds that it requires costimulation by B7 molecules. Specifically, blocking B7 molecules prevents the induction of anergy, maintaining T cells in a functionally competent state. The induction of anergy is further prevented by blocking CTLA-4, an inhibitory receptor that recognizes B7 molecules. This suggests that T cell tolerance is not due to a lack of costimulation but rather to specific recognition of B7 molecules by CTLA-4. In contrast, blocking CD28 on T cells prevents priming but does not affect the induction of tolerance. The results indicate that the outcome of antigen recognition by T cells is determined by the interaction between CD28 or CTLA-4 on T cells and B7 molecules on antigen-presenting cells (APCs). The findings have implications for understanding the mechanisms of T cell anergy and the regulation of immune responses.