Population movement and fate of autoreactive V beta 6+ T cells in Mls-1a mice.

In order to demonstrate the precise fail-safe mechanisms involved in the prevention of autoreactive T-cell functions, we analysed the movement of the population of self-reactive V beta 6+ cells in Mls-1a mice. T cells bearing V beta 6 T-cell receptor (TcR) could be detected in the thymus at birth. They increased in number during the next few days, then decreased and disappeared by 1 week after birth. These cells are autoreactive and capable of eliciting a syngeneic graft-versus-host reaction (GVHR). The autoreactive V beta 6+ cells in the thymus on day 3 were abolished by a previous injection of Mls-expressing syngeneic adult spleen cells, showing that the tolerance-inducing antigens had probably not yet developed in newborn mice. These autoreactive V beta 6+ cells escaping clonal deletion may leave the thymus and become appreciable as their percentages rise in the periphery in mice thymectomized 3 days after birth (d3-ThX). However, the 'autoreactive' T cells seemed to be neither cell cycling nor proliferating even after exogenous antigenic stimulation. The proportion of these peripheralized V beta 6+ cells in an 'anergy' state decreased gradually to a half-life of about 50 days in adults, in contrast to the complete deletion in a few days of V beta 6hi cells in the developing thymus. On the other hand, in weanlings the percentage of V beta 6+ T cells was reduced to a half-life of less than 20 days, probably because of the diluting out of these cells by the physiological expansion of the irrelevant T-cell population and probably by an increase of body fluid by a factor of 10. In contrast, V beta 8+ T cells, Mls-1a-unrelated, maintained a constant proportion, as in non-thymectomized mice. Thus, T-cell repertoire shaping may not always be achieved in the thymus, but may be completed after the cells leave the thymus a few days after birth in a developmentally programmed process.