ANALYSIS OF T-CELL REPOPULATION AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION - SIGNIFICANT DIFFERENCES BETWEEN RECIPIENTS OF T-CELL DEPLETED AND UNMANIPULATED GRAFTS

We have studied the repopulation of the T-cell compartment in 27 patie nts transplanted with bone marrow from an (HLA)-identical sibling. Sig nificant differences were found between recipients of unmanipulated an d T-cell depleted grafts. Analysis of the T cells by a method based on amplification of minisatellite DNA regions showed that without deplet ion >99.9% of the clones responding to a mitogenic stimulus after tran splantation were of donor origin. In contrast, when the graft had been depleted with Campath-1M plus complement, a significant part of the T cells cloned during the first weeks after transplantation comprised o f recipient T cells that had survived the preconditioning. This mixed population of low numbers donor and recipient T cells (19 +/- 31/mm(3) at day 14) expanded rapidly (predominantly CD8(+) T cells) during the first 2 months, without a significant change of the ratio of recipien t/donor T cells. In 11 of 17 evaluable patients a late wave (>9 months ) of donor T cells occurred. As a consequence, T-cell chimerism change d in favor of donor T cells and the CD4/CD8 ratio that had been revers ed (<0.5) after the first expansion, normalized (1.5 +/- 0.51). Analys is of the T-cell receptor repertoire showed that in recipients of a T- cell depleted graft, the recipient as well as the donor T cells that r epopulated the peripheral T-cell pool during the first month, were the progeny of a limited number of precursors. Because without depletion, when larger numbers of donor T cells had been cotransfused with the m arrow, the repertoire was much more diverse, these data show that imme diately after transplantation, the peripheral pool is repopulated prim arily through expansion of circulating T cells. (C) 1996 by The Americ an Society of Hematology.