DETERMINATION OF SPECIFIC IMMUNOLOGICAL TOLERANCE IN RADIATION CHIMERAS

Abstract

Various hemopoietic cell transfers from mouse radiation chimeras and from normal donors to irradiated recipients have been performed, and the reactivity of the spleen cells of the recipients against tissue antigens of both host type and of an unrelated type has been followed by means of the graft-versus-host assay in newborn mice. The state of specific tolerance to host-type tissues which is known to occur in certain radiation chimeras was lost on transfer of the tolerant bone marrow to a second host of a different antigenic constitution, and in several combinations specific tolerance towards the new host subsequently developed. This procedure could be repeated with the same line of cells. When tolerant bone marrow or spleen from radiation chimeras was retransferred to irradiated recipients of the original bone marrow donor strain, the tolerance also disappeared rapidly. Only when a large number of lymph node cells was transferred with the bone marrow was a temporary persistence of the specific tolerance observed in the spleen cells of the new host. Attempts to transfer immunity to tissue antigens with bone marrow, spleen and smaller numbers of lymph node cells have thus far failed. It is concluded that "memory" for the tolerant state is a property of the population of lymphoid cells being transferred and that the expression of this memory is dependent on the relative sizes of the populations. The results emphasize that the antigenic composition of the milieu in which the hemopoietic graft proliferates is one of the most important factors to determine the eventual immunological reactivity of the cell population derived from the donor. Furthermore the possibility is considered that tolerant cells may be at a disadvantage compared to potentially reactive cells as regards the repopulation of a depleted host. The implications of these results for the clinical application of foreign bone marrow transplantation have been discussed briefly.