Intrathymic restriction and peripheral expansion of the T-cell repertoire in Omenn syndrome

Simona Signorini, Luisa Imberti, Silvia Pirovano, Anna Villa, Fabio Facchetti, Marco Ungari, Fabio Bozzi, Alberto Albertini, Alberto G. Ugazio, Paolo Vezzoni, Luigi D. Notarangelo

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Abstract

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.

Original languageEnglish
Pages (from-to)3468-3478
Number of pages11
JournalBlood
Volume94
Issue number10
Publication statusPublished - Nov 15 1999

ASJC Scopus subject areas

  • Hematology

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    Signorini, S., Imberti, L., Pirovano, S., Villa, A., Facchetti, F., Ungari, M., Bozzi, F., Albertini, A., Ugazio, A. G., Vezzoni, P., & Notarangelo, L. D. (1999). Intrathymic restriction and peripheral expansion of the T-cell repertoire in Omenn syndrome. Blood, 94(10), 3468-3478.