title: Lack of iNKT cells in patients with combined immune deficiency due to hypomorphic RAG mutations.
abstract: Hypomorphic mutations of the RAG genes in humans are associated with a spectrum of clinical and immunologic presentations that range from T(-) B(-) severe combined immune deficiency (SCID) to Omenn syndrome. In most cases, residual V(D)J recombination activity allows for development of few T-cell clones, which expand in the periphery and infiltrate target organs, resulting in tissue damage. Invariant natural killer T (iNKT) cells play an important immunoregulatory role and have been associated with protection against autoimmunity. We now report on 5 unrelated cases of combined immune deficiency due to hypomorphic RAG mutations, and demonstrate the absence of iNKT cells in all 5 patients. These findings suggest that lack of this important immunoregulatory cell population may contribute to the pathophysiology of Omenn syndrome.
authors: Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors: Ponpan
authors: P
authors: Matangkasombut
authors: Muriel
authors: M
authors: Pichavant
authors: Doris E
authors: DE
authors: Saez
authors: Silvia
authors: S
authors: Giliani
authors: Evelina
authors: E
authors: Mazzolari
authors: Andrea
authors: A
authors: Finocchi
authors: Anna
authors: A
authors: Villa
authors: Cristina
authors: C
authors: Sobacchi
authors: Patricia
authors: P
authors: Cortes
authors: Dale T
authors: DT
authors: Umetsu
authors: Luigi D
authors: LD
authors: Notarangelo
mesh_terms: D045744:Cell Line, Tumor; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D017354:Point Mutation; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein