Abrogation of secondary skin allograft rejection by veto-like cells in donor bone marrow.

Abstract

To investigate whether a veto cell phenomenon is involved in the ability of donor strain bone marrow cells (BMC) to inactivate second-set skin graft rejection induced by the adoptive transfer of sensitized spleen cells (SSC), mice were grafted with ear skin allografts and injected on the following day with recipient strain SSC or SSC plus donor strain BMC. When skin and BMC donors from an F1 strain (B6AF1) were combined with a parental strain (C57BL/6) as recipient and SSC donors, the BMC were fully active in abrogating second-set rejection even though the SSC were naturally tolerant of the BMC. Thus, immunological recognition of the SSC by the BMC is not necessary for this abrogation. The suppressive activity of the BMC is specific in a manner similar to that reported for veto cells (i.e., they suppress an anti-self response). If BMC from various strains of mice were used to alter the rejection of C3H grafts by B6AF1 recipients, only BMC expressing the MHC antigens to which the SSC had been sensitized significantly suppressed the activity of SSC. Sharing of additional antigens between the graft and BMC (e.g., MHC antigens not recognized by the SSC or minor antigens) was neither necessary nor sufficient. Mitomycin C-treated BMC were unable to inhibit SSC-induced accelerated rejection. Overall, the characteristics of the SSC-suppressive activity of BMC are consistent with a veto cell nature of the BMC.