Human TCR {alpha}/{beta}+ CD4-CD8- Double-Negative T Cells in Patients with Autoimmune Lymphoproliferative Syndrome Express Restricted V{beta} TCR Diversity and Are Clonally Related to CD8+ T Cells. - Archive ouverte HAL Access content directly
Journal Articles Journal of Immunology Year : 2008

Human TCR {alpha}/{beta}+ CD4-CD8- Double-Negative T Cells in Patients with Autoimmune Lymphoproliferative Syndrome Express Restricted V{beta} TCR Diversity and Are Clonally Related to CD8+ T Cells.

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Abstract

The peripheral expansion of alpha/beta(+)-CD4(-)CD8(-) double negative (DN) T cells in patients with autoimmune lymphoproliferative syndrome (ALPS) is a consistent feature of this disease, and part of the diagnostic criteria of ALPS. The origin of these cells remains undetermined. They could derive from mature T cells that have lost coreceptor expression, or represent a special minor cell lineage. To investigate relationship of DN and single positive (SP) T cells in ALPS, we used Immunoscope technology to analyze the TCRVbeta repertoire diversity of sorted DN and SP T cells, and we performed CDR3 sequence analyses of matching clonotypes. We show that DN T cells express all the Vbeta gene families that are used by their SP counterparts, though they dominantly use some Vbeta genes. Analysis of CDR3 length distribution revealed a diverse polyclonal TCR repertoire for sorted CD4(+) T cells, whereas both DN and CD8(+) T cells showed a skewed TCR repertoire with oligoclonal expansions throughout most of the Vbeta families. CDR3 sequencing of matching clonotypes revealed a significant sharing of CDR3 sequences from selected Vbeta-Jbeta transcripts between DN and CD8(+) T cells. Altogether, these data strongly argue for a CD8 origin of DN T cells in ALPS.
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Dates and versions

pasteur-00293060 , version 1 (03-01-2009)

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Anne Bristeau-Leprince, Véronique Mateo, Annick Lim, Aude Magerus-Chatinet, Eric Solary, et al.. Human TCR {alpha}/{beta}+ CD4-CD8- Double-Negative T Cells in Patients with Autoimmune Lymphoproliferative Syndrome Express Restricted V{beta} TCR Diversity and Are Clonally Related to CD8+ T Cells.. Journal of Immunology, 2008, 181 (1), pp.440-8. ⟨10.4049/jimmunol.181.1.440⟩. ⟨pasteur-00293060⟩
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