期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 1, 页码 440-448出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.1.440
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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 TCRV beta 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 V beta gene families that are used by their SP counterparts, though they dominantly use some V beta 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 V beta families. CDR3 sequencing of matching clonotypes revealed a significant sharing of CDR3 sequences from selected V beta-J beta 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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