CD4(-CELLS ANERGIZED BY HIGH-DOSE FEEDING ESTABLISH ORAL TOLERANCE TOANTIBODY-RESPONSES WHEN TRANSFERRED IN SCID AND NUDE-MICE() T)

The cellular mechanism for oral tolerance in specific Ab response was investigated by cell-transfer experiments, using severe combined immun odeficiency (SCID) and BALB/c nu/nu mice. High dose feeding with bovin e alpha(s1)-casein, a major allergen in milk, to BALB/c mice induced A g-specific oral tolerance to the specific Ab response. This stale of o ral tolerance was successfully transferred to SCID mice with splenocyt es from orally tolerant BALB/ce mice. In SCID mice that were transferr ed with tolerant T cells and normal B cells before being immunized wit h alpha(s1)-casein, oral tolerance to the Ab responses was generated. In addition, only the T cells established the tolerant state in nude m ice. A decreased proliferative response of the splenic T cells from BA LB/c mice against alpha(s1)-casein was also shown, indicating that the decreased Ab responses were attributed to the unresponsiveness of the splenic T cells. Next, the tolerant splenic T cells were further sepa rated into CD4(+) T cells and CD8(+) T cells, remixed with normal cell s, and then transferred to nude mice, which revealed that the tolerant state in the nude mice was principally generated by the CD4(+) T cell s. When tolerant CD4(+) T cells were cotransferred with normal CD4(+) T cells to nude mice, there was no significant reduction in the specif ic Ab responses. These results demonstrate that splenic CD4(+) T cells anergized by high dose feeding established oral tolerance to the Ab r esponses when transferred to SCID and nude mice.