Specific helper T cell reactivity against autologous erythrocytes implies that self tolerance need not depend on clonal deletion.

Using a culture system which supports primary T cell proliferative responses to various antigens we have detected mouse red blood cell (RBC)-reactive T cells in lymphoid tissues from untreated mice. The release of significant amounts of interleukin 2 (IL2) indicates that T helper (or helper/inducer) cells are activated by stimulation with RBC. Upon restimulation in vitro these cells proliferate specifically against mouse RBC with the kinetics and magnitude characteristic of a secondary response. Since autologous RBC are tolerated in vivo in spite of the presence of such specifically reactive T helper cells, these findings imply that self tolerance, even to certain nonsequestered antigens, may depend largely on regulatory mechanisms rather than on clonal deletion or inactivation.