B-CELLS ARE NOT ESSENTIAL FOR PERIPHERAL T-CELL TOLERANCE

Some self-reactive T cells avoid thymic tol erance and become mature p eripheral cells. Nevertheless, these cells do not usually attack their hosts because T cells can be inactivated or killed, even after they a re mature, by various means. The details of these processes are not fu lly understood; however, a number of experiments have suggested that p eripheral tolerance may be induced in mature mouse T cells by exposure to antigen on resting B cells, cells that can express antigen bound t o major histocompatibility complex proteins but that lack critical cos timulatory molecules such as B7-1 and B7-2. Conversely, previous exper iments have indicated that mature T cells can be stimulated by exposur e to antigen on cells such as dendritic cells, cells that are thought to express the essential costimulatory molecules. We tested this idea in vivo by using mice that lack B cells. Unexpectedly, T-cell toleranc e and antigen-induced T-cell death occurred normally in mice free of B cells. On the other hand, antigen-specific T-cell expansion in the sp leens of such mice was impaired. Finally, we have recently shown that T-cell death in mice can be prevented by exposure to antigen and an in flammatory agent such as bacterial lipopolysaccharide. This was also t rue in mice that lacked B cells. Overall, these data show that mature T cells can be tolerized and rescued from tolerance in the absence of B cells.