INVESTIGATIONS OF IMMUNOLOGICAL TOLERANCE IN TETRAPARENTAL MOUSE CHIMAERAS

Abstract

SUMMARY The tetraparental model was used to investigate the mechanism of induction and maintenance of tolerance. Of eight C57BL?BALB/c, potential tetraparental mice, six were found to be chimaeric by coat colour and by one or more of the following parameters: g.p.i., γ2a allotype testing, lymphocytotoxicity testing and germ line. None of the mice were chimaeric by all of these tests but showed instead a variable spectrum of chimaerism. Tolerance was investigated by both in vivo and in vitro testing. When the mice were chimaeric by at least two criteria, they were unresponsive to skin allografting (five out of six mice) and their spleen cells were non‐reactive against BALB/c × C57BL F1 s in the popliteal node GVH, test. In contrast, the MLRs were generally positive and could not be blocked by chimaera serum or suppressed by chimaera thymus suspensions. Thus while we cannot formally exclude a suppressive mechanism, our results are best explained by the classical theory of clonal elimination provided one accepts that clonal reactivity and elimination is heterogeneous. The very establishment of a successful chimaera may be dependent upon the elimination of clones causing lethal GVHR while those responsible for an MLR or other non‐lethal parameters of chimaerism is retained.