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2018 ; 9
(ä): 389
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Potential Beneficial Effects of Cytomegalovirus Infection after Transplantation
#MMPMID29545802
Litjens NHR
; van der Wagen L
; Kuball J
; Kwekkeboom J
Front Immunol
2018[]; 9
(ä): 389
PMID29545802
show ga
Cytomegalovirus (CMV) infection can cause significant complications after
transplantation, but recent emerging data suggest that CMV may paradoxically also
exert beneficial effects in two specific allogeneic transplant settings. These
potential benefits have been underappreciated and are therefore highlighted in
this review. First, after allogeneic hematopoietic stem cell transplantation
(HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK)
cell-replete grafts, CMV reactivation is associated with protection from leukemic
relapse. This association was not observed for other hematologic malignancies.
This anti-leukemic effect might be mediated by CMV-driven expansion of
donor-derived memory-like NKG2C(+) NK and V?2(neg??) T-cells. Donor-derived NK
cells probably recognize recipient leukemic blasts by engagement of NKG2C with
HLA-E and/or by the lack of donor (self) HLA molecules. V?2(neg??) T cells
probably recognize as yet unidentified antigens on leukemic blasts via their TCR.
Second, immunological imprints of CMV infection, such as expanded numbers of
V?2(neg??) T cells and terminally differentiated TCR??(+) T cells, as well as
enhanced NKG2C gene expression in peripheral blood of operationally tolerant
liver transplant patients, suggest that CMV infection or reactivation may be
associated with liver graft acceptance. Mechanistically, poor alloreactivity of
CMV-induced terminally differentiated TCR??(+) T cells and CMV-induced IFN-driven
adaptive immune resistance mechanisms in liver grafts may be involved. In
conclusion, direct associations indicate that CMV reactivation may protect
against AML relapse after allogeneic HSCT, and indirect associations suggest that
CMV infection may promote allograft acceptance after liver transplantation. The
causative mechanisms need further investigations, but are probably related to the
profound and sustained imprint of CMV infection on the immune system.
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