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  • Title: A SCID patient reconstituted with HLA-incompatible fetal stem cells as a model for studying transplantation tolerance.
    Author: Roncarolo MG, Bacchetta R, Bigler M, Touraine JL, de Vries JE, Spits H.
    Journal: Blood Cells; 1991; 17(2):391-402. PubMed ID: 1680508.
    Abstract:
    We studied a severe combined immunodeficiency (SCID) patient who received transplantations 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.
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