A dual lineage model for the development of mature human NK-cells(2/3)

There are 2 major subtypes of mature NK-cells with differential surface markers in the
peripheral blood, CD56 + KIR +/- Lectin + and CD56 +/- KIR + Lectin +/- . Our proposal is aimed at
clarifying the developmental pathway of these 2 subtypes of mature NK-cells. So far, we have
achieved the following:
I: Isolation and expansion of CD34 + stem cells from umbilical cord blood
We have isolated CD34 + stem cells from umbilical cord. We are able to expand the CD34 + Lin-
stem cells with the use of an in vitro culture system under cytokine stimulation. An 5-10 fold
expansion is achieved after 1-week culture.
II: Partial Induction of CD56 expression, suggestive of NK-differentiation
The expanded stem cells were further grown for another 1 week, to induce differentiation.
Although most cells developed into the myeloid lineage, about 5-10% were CD56 + , suggestive
of an NK-lineage. To continue the investigation, we are currently using IL-15 to stimulate
proliferation and induction of mature NK-cells.
III: Confirmation of lineage assignment of sinonasal lymphoma
We have performed an extensive assessment of the lineage assignment of sinonasal
lymphomas. We found most sinonasal lymphomas had a restricted killer immunoglobulin-like
receptor repertoire, consistent with a NK-lineage. But some cases had a monoclonal T-cell
receptor rearrangement plus a restricted killer immunoglobulin-like receptor repertoire, consistent
with a mixed NK/T cell lineage. (Am J Path, 2001, 159, 1671.)
IV: Clinical correlation and significance.
Further analysis of the expression pattern of CD94 (the killer lectin-like receptor) showed
that a subset of sinonasal lymphoma had CD94 expression. The CD94 positive subset had a much
better prognosis than the CD94-negative subset. (Blood, 2003, 102, 2623) We are currently
investigating whether these 2 subsets correspond to the 2 major subsets of mature NK-cells
of the peripheral blood.