INDUCTION OF ORAL TOLERANCE IN SPLENOCYTE-RECONSTITUTED SCID MICE

The participation of each lymphocyte compartment in the induction of o ral tolerance for antibody response was investigated by means of a new cell-transfer experimental system, using severe combined immunodefici ency (SCID) mice. Various lymphocyte compartments from BALB/c mice wer e transferred into SCID mice and these mice were evaluated for oral to lerance induction. First, whole splenocytes from BALB/c mice were tran sferred into SCID mice and these mice were orally administered bovine a,l-casein. The specific antibody response in these mice after subsequ ent immunization with antigen was greatly reduced compared to controls which were not fed the antigen, and it was demonstrated that oral tol erance was induced in SCID mice bearing donor splenocytes. Oral tolera nce was induced in SCID mice that were reconstituted with only T cells , revealing that B cells were not required for the induction of oral t olerance. Further, oral tolerance was induced in SCID mice reconstitut ed with CDS-depleted splenocytes but not in mice reconstituted with on ly CD8(+) T cells. These results demonstrate that oral tolerance could be induced in SCID mice bearing normal splenocytes and that interacti on of CD4(+) T cells with antigen-presenting cells other than B cells are responsible for the induction of oral tolerance. Our experimental system may be useful for investigations with human lymphocytes, (C) 19 98 Academic Press.