Intrathymic induction of neonatal tolerance to Mls-1a determinant: clonal deletion and clonal anergy by haematolymphoid cells

Abstract

Newborn BALB/c (Mls-1b) mice were intravenously injected with either bone marrow cells (BMC) or peritoneal exudate cells (PEC) from Mls semi-allogeneic (BALB/c x AKR)F1 mice. Thymic cells of these mice, obtained 7 days after the injection, were found to be unresponsive to the superantigen Mls-1a, as determined by graft-versus-host reactivity. On Day 7, deletion of T cells expressing the V beta 6 element at high levels (V beta 6hi) was observed in thymic cells of mice receiving PEC. In mice given BMC, it took 2 weeks until the proportion of V beta 6hi T cells began to decline, and a longer period was required for complete disappearance of V beta 6hi T cells. These results may indicate that although both BMC and PEC contain cells mediating tolerance, a component(s) of cells responsible for clonal deletion is deficient in BMC. Immunohistological investigation showed that on Day 7 donor type B cells were present in the thymus of mice that received PEC but absent from mice that received BMC, whereas cells expressing donor type class I as well as class II antigens were seen in both recipients. The presence of donor type B cells could be observed 8 weeks after injection of BMC. By this time, the deletion of V beta 6hi T cells was completed. These results indicate, collectively, that the tolerance of both anergy type and deletion type occurs in the naturally developing thymus, and suggest that the presence of B cells in the thymus might be required for clonal deletion.