A SCID patient reconstituted with HLA-incompatible fetal stem cells as a model for studying transplantation tolerance

M. G. Roncarolo, R. Bacchetta, M. Bigler, J. L. Touraine, J. E. De Vries, H. Spits

Research output: Contribution to journalArticlepeer-review

Abstract

We studied a severe combined immunodeficiency (SCID) patient who received transplantation with completely HLA-mismatched fetal liver and thymus from two different donors. The patient is now 14 years old, healthy and shows normal immunoresponses to recall antigens. His T cells are of donor origin, whereas the monocytes, B cells, and natural killer (NK) cells are of the recipient. The successful immunological reconstitution raised questions as to how T and B cells could collaborate across an HLA barrier and how tolerance was achieved. We have shown that tetanus toxin-specific T cell clones isolated from this patient recognized this antigen in the context of host and not of donor HLA-DR, indicating that those cells were educated in the host environment, presumably the thymus. Despite this, an unexpectedly high frequency of host-reactive clones was found that could recognize MHC antigens of the host. It was particularly striking that CD8+ CTL clones were obtained that recognized class I MHC antigens on the host cells. Nevertheless, the patient did not show any sign of acute or chronic graft-versus-host disease (GVHD). These data indicated that no or only incomplete clonal deletion had taken place in this patient and suggest the presence of a peripheral suppressor mechanism. Thus far, we have no indication for the existence of suppressor T cells. Inasmuch as it was found that host-reactive T cells fail to produce IL-4, which is exceptional for CD4+ T cells, we are exploring the possibility that abnormal cytokine production patterns of host-reactive T cells are associated with suppression of these cells in vivo.

Original languageEnglish
Pages (from-to)391-402
Number of pages12
JournalBlood Cells
Volume17
Issue number2
Publication statusPublished - 1991

Keywords

  • Cellular cooperation
  • FLTT
  • SCID
  • Tolerance

ASJC Scopus subject areas

  • Hematology

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