Influence of Fetomaternal Microchimerism on Maternal NK Cell Reactivity against the Child's Leukemic Blasts
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Influence of Fetomaternal Microchimerism on Maternal NK Cell Reactivity against the Child's Leukemic Blasts. / Martin, Lena-Marie; Kruchen, Anne; Fehse, Boris; Müller, Ingo.
In: BIOMEDICINES, Vol. 10, No. 3, 603, 04.03.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Influence of Fetomaternal Microchimerism on Maternal NK Cell Reactivity against the Child's Leukemic Blasts
AU - Martin, Lena-Marie
AU - Kruchen, Anne
AU - Fehse, Boris
AU - Müller, Ingo
PY - 2022/3/4
Y1 - 2022/3/4
N2 - Persistence of fetal cells in the circulation of the mother (fetal microchimerism, FM) is associated with increased survival and reduced relapse of children with leukemia receiving a haploidentical hematopoietic stem cell transplantation (hHSCT). NK cells play an important role in maternal tolerance towards the unborn child. In this study, 70 mother-child pairs were prospectively analyzed for the occurrence of FM, KIR genotype and HLA-C type. We found that occurrence and level of FM were influenced by three maternal genetic factors: presence of an HLA-C1 allele, absence of KIR2DL3 and presence of a cen-B/B motif. Furthermore, an HLA-C match between mother and child favored persistence of FM. NK cells from FM+ mothers showed a 40% higher specific degranulation against their filial leukemic blasts than NK cells from FM- mothers, suggesting the presence of educated maternal NK cells. Nevertheless, cytotoxicity of parental NK cells against filial leukemic blasts was independent of KIR genetics (haplotype, B content score, centromeric and telomeric KIR gene regions) and independent of FM, indicating that additional immune effector mechanisms contribute to the beneficial effect of persisting FM in hHSCT.
AB - Persistence of fetal cells in the circulation of the mother (fetal microchimerism, FM) is associated with increased survival and reduced relapse of children with leukemia receiving a haploidentical hematopoietic stem cell transplantation (hHSCT). NK cells play an important role in maternal tolerance towards the unborn child. In this study, 70 mother-child pairs were prospectively analyzed for the occurrence of FM, KIR genotype and HLA-C type. We found that occurrence and level of FM were influenced by three maternal genetic factors: presence of an HLA-C1 allele, absence of KIR2DL3 and presence of a cen-B/B motif. Furthermore, an HLA-C match between mother and child favored persistence of FM. NK cells from FM+ mothers showed a 40% higher specific degranulation against their filial leukemic blasts than NK cells from FM- mothers, suggesting the presence of educated maternal NK cells. Nevertheless, cytotoxicity of parental NK cells against filial leukemic blasts was independent of KIR genetics (haplotype, B content score, centromeric and telomeric KIR gene regions) and independent of FM, indicating that additional immune effector mechanisms contribute to the beneficial effect of persisting FM in hHSCT.
UR - https://www.mdpi.com/2227-9059/10/3/603
U2 - 10.3390/biomedicines10030603
DO - 10.3390/biomedicines10030603
M3 - SCORING: Journal article
VL - 10
JO - BIOMEDICINES
JF - BIOMEDICINES
SN - 2227-9059
IS - 3
M1 - 603
ER -