The Thymus: Its Influence on Recognition of “Self Major Histocompatibility Antigens” by T Cells and Consequences for Reconstitution of Immunodeficiency

  • Rolf M. Zinkernagel


It has become clear that severe combined immunodeficiency (SCID) is a heterogeneous group of congential disorders and, similarly, that thymus hypoplasia or deficiency may have various aetiologies [1–4]. Thus, immunodeficiency can result if the thymus either fails to produce thymic hormone or fails to provide adequate epithelial cell-cell contact mechanisms to induce T cell differentiation. Stem cells may also be defective and cause immunodeficiency either because they are blocked in their normal differentiation programs or because they fail to enter the thymus or circulate properly through [5, 6]. Attempts at reconstituting immunodeficient patients by administering fetal thymus or stem cells have met with variable success. Immunocompetence may be restored to the degree that such patients responded to stimulation with PHA or rejected foreign skin grafts; unfortunately, in some cases they showed no increase in antibody production nor any lessening of their high susceptibility to infectious disease [1, 7–12]. In most of the clinical attempts at reconstitution, bone marrow transplants were HLA matched with the recipient, but not thymic or fetal liver cells [1]. The reasoning was that these fetal organs and cells were taken before immunocompetency was reached; therefore, a graft-versus-host disease was not possible [1–4]. Our hypothesis and experimental model in mice may offer an explanation for the variable therapeutic successes with fetal grafts and may reveal a basis for establishing improved rules for cellular engineering in reconstituting immunodeficient patients.


Mixed Lymphocyte Reaction Severe Combine Immunodeficiency Severe Combine Immunodeficiency Disease Fetal Liver Cell Lymphocytic Choriomeningitis 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1979

Authors and Affiliations

  • Rolf M. Zinkernagel
    • 1
  1. 1.Department of Cellular and Developmental ImmunologyScripps Clinic and Research FoundationLa JollaUSA

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