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repertoires between unmanipulated BM transplants and T-cell-depleted
transplants. T-cell depletion was mediated through anti-thymocyte globu-
lin, elutriation, or campath. They found that KIR expression was increased
in the patients who received T-cell-depleted grafts. Furthermore the pres-
ence of T cells in the graft was correlated with increased GVHD and worse
outcomes. However, Nguyen and colleagues [83] were able to demonstrate a
beneficial effect of T cells in the graft. Looking at haploidentical HSCT they
compared partial and complete T-cell depletion. Recipients who received
partial T-cell-depleted grafts had lower expression of NKG2A, similar cyto-
toxicity against K562 compared with donor NK cells, and higher cytotoxicity
against AML blasts compared with recipients who received complete T-cell-
depleted grafts. Recipients who received complete T-cell-depleted grafts had
higher IFN-γ responses when stimulated with IL-12 and IL-18, which is to
be expected as CD56 bright NKG2A + NK cells are more responsive to IL-12 and
IL-18 stimulation [84] . These findings contradict earlier reports that T cells
in the graft hinder NK cell function. This was further confirmed by a study
from Foley and colleagues [85] that compared NK cell function (cytotoxicity
and cytokine production) following HSCT with three different graft preps,
unmanipulated (T-cell replete), CD34 + selected (T-cell depleted) without
post-transplant immune suppression, and UCB. Overall NK cell function
was lower following HSCT compared with donor NK cells. Surprisingly, how-
ever, NK cell function was highest following T-cell-replete HSCT and this was
associated with higher KIR expression. In recipients of T-cell-replete HSCT,
it was demonstrated that target-induced IFN-γ production was associated
with KIR and not NKG2A, as NK cells expressing only NKG2A were poor pro-
ducers of IFN-γ. Furthermore IFN-γ-producing NK cells expressed a KIR that
recognized self. As NKG2A-expressing NK cells were cytotoxic, it was pos-
tulated that in the post-transplant setting, the interaction between NKG2A
and HLA-E supports the education of NK cells to degranulate but that the
signal is too weak to meet the threshold to educate for cytokine production.
Therefore these studies collectively suggest that T cells may actually be ben-
eficial in promoting NK cell function rather than hindering it. Activated T
cells produce IL-2, which has been shown to stimulate CD56 bright NK cells
in the lymph nodes to produce IFN-γ and to contribute to NK cell maturity
[86] . Alternatively, donor NK cells may persist in the recipient for longer than
originally reported and infused mature donor NK cells may contribute to the
increased function seen after T-cell-replete HSCT.
342
UCB transplants have become a viable alternative to BM or peripheral blood
HSCT. Because of the low number of mature T cells present, the risk of acute
GVHD is low and therefore HLA-mismatched units are frequently used.
Despite being able to mediate cytotoxicity and induce apoptosis through
Fas/FasL [87] , NK cells reconstituting after UCB transplant are poor pro-
ducers of IFN-γ [85] . Incomplete recovery of full NK cell effector functions
may be involved in the high incidence of viral infections compared with the
other types of transplant [88] .
As described earlier, NK cells acquire function through a process known as
NK cell education. How NK cell education influences NK cell function post-
HSCT has only recently been investigated. Can an NK cell that expresses an
inhibitory receptor for a nonself ligand be educated in the recipient, if the
recipient sees that receptor as self, or will it remain hyporesponsive? Yu and
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