Rationale for combined use of fetal liver and thymus for immunological reconstitution in patients with variants of severe combined immunodeficiency.

Overview

Bone marrow cells from a patient with severe combined immunodeficiency were studied in vitro for thymus-dependent lymphocyte (T cell) differentiation by using, at varying times, thymic epithelial monolayers and culture supernatants, thymopoietin, ubiquitin, and thymic extract as inducing agents. On initial evaluation, with thymopoietin or human thymic extract, only a partial differentiation of marrow cells was achieved into cells bearing the human T cell antigenicity without the capacity to form rosettes with sheep erythrocytes, suggesting that the stem cells were defective. Two fetal liver transplantations aimed at reconstitution were unsuccessful, despite evidence of chimerism. Induction studies at that time demonstrated rosetting capacity (with sheep erythrocytes) of the patient's bone marrow cells after coculture with thymic epithelial monolayers but not with their supernatants. An 18-week fetal thymus (irradiated) was then transplanted, but the transplantation was unsuccessful and no clear evidence of chimerism was demonstrated. Subsequently, transplantation of another fetal liver resulted in chimerism and immunologic reconstitution. Serum thymic factor activity rose from 1:2 before transplantation to 1:16 after reconstitution. The combined use of fetal thymus and liver may provide effective immunological reconstitution in some variants of severe combined immunodeficiency.