Nondeletional mechanisms of tolerance in total-lymphoid irradiation-induced bone marrow chimeras

To directly determine whether deletion mechanisms maintain tolerance after TLI, we applied the well-described negative selection phenomena of specific TCR bearing cells by Mls antigen to our TLI-prepared bone marrow chimeras (TLI-BMC)*. We chose DBA/2 mice as the host strain and CBA/CaJ as the donor strain because DBA/2 (Mls-1 super(a), Mls-2 super(a)) but not CBA/CaJ (Mls-1 super(b), Mls-2 super(b)) mice express Mls antigen and delete T cells that bear V beta 8.1 and V beta 3 T cell receptors. Staining of spleen cells in chimeras with monoclonal antibody against specific TCR determined the presence or absence of V beta 3 or V beta 8.1 T cells. If maintaining tolerance involves deletion mechanisms, then the percentage of V beta 3 and V beta 8.1 T cells in spleens from chimeras would resemble the V beta 3 and V beta 8.1 percentage from host DBA/2 mice. If the number of V beta 3 or V beta 8.1 cells resembles the CBA/CaJ host, then chimeras fail to delete potentially "autoreactive" T cells, and anergy or suppression mechanisms maintain tolerance.