CD45RC(-CELL SUBSETS ARE MAINTAINED IN AN UNRESPONSIVE STATE BY THE PERSISTENCE OF TRANSFUSION-DERIVED ALLOANTIGEN() CD4 T)

The ability of preoperative blood transfusion to extend the survival o f organ allografts is well known but poorly understood. To study this phenomenon, adult PVG (RT1(c)) rats were rendered tolerant of DA (RT1( a)) cardiac allografts by prior donor-specific blood transfusion (DST) . We investigated the cellular basis of the transfusion effect by adop tively transferring CD4 T cell subsets, obtained from thoracic duct ly mph of tolerant rats, into cardiac allografted athymic PVG nude recipi ents. Surprisingly, CD4 T cells hom DST rats evoked acute rejection on adoptive transfer. Evidence indicated that CD8 T cells played no role in DST-induced tolerance. Analysis of CD4 T cell subsets, defined in the rat by mAb OX22 (anti-CD45RC), revealed an unusual pattern of resp onsiveness. CD45RC(+) CD4 T cells (normally capable of inducing prompt rejection), when obtained from rats given a specific blood transfusio n, were depleted of alloreactive cells and deficient at inducing rejec tion. In contrast, the CD45RC(-) subset (normally slow at evoking graf t destruction) was highly active and ten-fold-enriched in its ability to induce rejection. Destruction of cardiac allografts by this latter subset was, however, completely inhibited by giving nude recipients a specific (but not a third-party) blood transfusion two weeks before he art grafting and cell transfer. Apparently, tolerance was maintained b y residual elements of the prior blood transfusion that prevented the specific CD45RC(-) subset from regaining an alloaggressive capacity.