Abstracts (complete list) - Wissenschaft Online

Manfred Hönig, Ansgar Schulz, Catharina Schütz, Paul Fisch, Tatjana Kersten, Ulrich
Pannicke, Markus Rojewski, Wilhelm Friedrich, Klaus Schwarz
Somatic reversion of lymphocyte subpopulations after HSCT
in a patient with JAK3 deficiency -Evidence for independent
αβ- and γδ- T-lineage stem cells
Spontaneous somatic reversions are reported for various immunodeficiencies (e.g.
IL2RG, ADA, WAS, RAG1, Artemis, LAD1). We report on a 14 year old girl with SCID
due to JAK3 deficiency, who was treated in infancy by HLA-haploidentical
haematopoietic stem cell transplantation (HSCT) without conditioning. A functional
donor T cell system was established. 10 years after HSCT, a small amount (10%) of
autologous T cells was noted in addition to donor T cells in routine chimerism analysis.
Reversions of both compound heterozygous point mutations (NM_000215: c.424C>T,
c.1351C>T leading to NM_00026: p.[Arg142Cys]+[Arg451X] ) to wild type (wt) -
sequence were found in this autologous T-cell population: &alpha&beta-TCR positive T
cells (and NK cells) are reverted to wt-sequence in Exon4, whereas &gamma&delta-TCR
positive T cells are reverted in the other affected allele (Exon9). The TCR-repertoires of
these T-cell populations are oligoclonal. The reversions thus must have occurred before
TCR-rearrangement but after the determination of an &alpha&beta- or &gamma&delta-
T-cell fate. These findings strongly support a non-instructive model for this decision in Tcell
development.