title: Depletion of CD8+ cells in human thymic medulla results in selective immune deficiency.
abstract: CD8 molecules expressed on the surface of a subset of T cells participate in the selection of class I MHC antigen-restricted T cells in the thymus, and in MHC-restricted immune responses of mature class I MHC antigen-restricted T cells. Here we describe an immune-deficient patient with lack of CD8+ peripheral blood cells. The patient presented with Pneumocystis carinii pneumonia and was unable to reject an allogeneic skin graft, but had normal primary and secondary antibody responses. Examination of the patient's thymus revealed that the loss of CD8+ cells occurred during intrathymic differentiation: the patient's immature cortical thymocytes included both CD4+ and CD8+ cells while the mature medullary cells expressed the CD4 but not the CD8 protein on their surface. Northern blot and polymerase chain reaction analyses revealed the presence of CD8 alpha and beta mRNA in the patient's thymus but not in the peripheral blood. Both class I MHC antigen expression and the expressed TCR V beta repertoire are normal in this patient. These data are consistent with an impaired selection of CD8+ cells in the patient's thymus and support the role of the CD8 surface protein in thymic selection previously characterized in genetically manipulated and inbred mice.
authors.affiliation: Division of Immunology/Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Roifman
authors.forename: D
authors.initials: D
authors.lastname: Hummel
authors.forename: H
authors.initials: H
authors.lastname: Martinez-Valdez
authors.forename: P
authors.initials: P
authors.lastname: Thorner
authors.forename: P J
authors.initials: PJ
authors.lastname: Doherty
authors.forename: S
authors.initials: S
authors.lastname: Pan
authors.forename: F
authors.initials: F
authors.lastname: Cohen
authors.forename: A
authors.initials: A
authors.lastname: Cohen
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D016827:CD8 Antigens; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D007223:Infant; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell