Cooperation Between Thymus and Transplanted Precursor Cells During Reconstitution of Immunodeficiencies with Bone Marrow or Fetal Liver Cells

Abstract

The role of the thymus in the immunological reconstitution following transplantation of bone marrow or spleen cells in irradiated mice has been unequivocally established. The development of bone marrow transplantation in man for the treatment of severe combined immunodeficiency diseases (SCID), aplastic anemias and leukemias, over the last two decades has also demonstrated the importance of normal thymic function for complete immune reconstitution. The transplant of even less mature precursor cells, such as those contained in the fetal liver, leads to a slower T-cell maturation and the role of the thymus is still more crucial in such circumstances. It can thus be noted that combined thymus and liver cells from the same fetus are more efficient in reconstituting immunodeficient children than mere fetal liver cells. Several questions, of obvious practical significance, remain, however, unresolved: Are thymic epithelial cells necessary or can thymic factors replace the thymus organ? What are the thymic lesions in the diseases treated with marrow or fetal liver transplantation and are those lesions rapidly reversible? At which differentiation stages is the thymus more necessary? When the thymus expresses HLA antigens different from those of the lymphoid cells, does it induce an “allogeneic restriction” specific of the thymus type, will T cell functions be limited in a HLA-different host and will T cells be unable to cooperate with different B cells?