Intrathymic Restriction and Peripheral Expansion of the T-Cell Repertoire in Omenn Syndrome
| Autor: | Luigi D. Notarangelo, Anna Villa, Paolo Vezzoni, Silvia Pirovano, Fabio Bozzi, Alberto G. Ugazio, Alberto Albertini, Marco Ungari, Simona Signorini, Luisa Imberti, Fabio Facchetti |
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| Rok vydání: | 1999 |
| Předmět: |
DNA repair
T-Lymphocytes Molecular Sequence Data Immunology Receptors Antigen T-Cell Thymus Gland Biology medicine.disease_cause Biochemistry Peripheral blood mononuclear cell Immune system Antigen Sequence Homology Nucleic Acid medicine Humans Homeodomain Proteins Mutation Base Sequence T-cell receptor Immunologic Deficiency Syndromes Infant Newborn Genetic Variation Nuclear Proteins Cell Biology Hematology T lymphocyte medicine.disease Omenn syndrome DNA-Binding Proteins Leukocytes Mononuclear Female |
| Zdroj: | Scopus-Elsevier Europe PubMed Central |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v94.10.3468.422k34_3468_3478 |
| Popis: | Mutations in the human RAG genes that impair, but do not abolish, recombination activity lead to Omenn syndrome, a severe primary immune deficiency that is associated with clinical and pathological features of graft-versus-host disease and oligoclonal expansion of activated, autologous T cells. We have analyzed the mechanisms accounting for peripheral oligoclonality of the T-cell repertoire. Predominance of few T-cell receptor clonotypes (both within TCRAB- and within TCRGD-expressing lymphocytes) is already detectable in the thymus and is further selected for in the periphery, with a different distribution of clonotypes in different tissues. These data indicate that oligoclonality of the T-cell repertoire in Omenn syndrome is due both to intrathymic restriction and to peripheral expansion. Moreover, the RAG genes defect that causes Omenn syndrome directly affects early stages of V(D)J recombination, but does not alter the process of double-strand-break DNA repair, including N and P nucleotide insertion. |
| Databáze: | OpenAIRE |
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