Lack of iNKT cells in patients with combined immune deficiency due to hypomorphic RAG mutations.
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.
Matangkasombut
Ponpan
P
Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Pichavant
Muriel
M
Saez
Doris E
DE
Giliani
Silvia
S
Mazzolari
Evelina
E
Finocchi
Andrea
A
Villa
Anna
A
Sobacchi
Cristina
C
Cortes
Patricia
P
Umetsu
Dale T
DT
Notarangelo
Luigi D
LD
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
D018398:Homeodomain Proteins; C064658:RAG-1 protein