Differential effect of pretransplant blood transfusions on immune effector and regulatory compartments in HLA-sensitized and nonsensitized recipients

BACKGROUND: Blood transfusion (BT) may elicit both harmful and beneficial immune responses against a subsequent organ graft. Immune parameters of a single, non leukocyte-depleted BT were investigated in two groups: non-human leukocyte antigen (HLA)-sensitized recipients with a one-HLA-DR matched donor (protocolled BT [PBT]) and females with previous exposure to HLA alloantigens through pregnancy (donor-specific transfusion [DST]).

METHODS: Thirty-five percent of DST recipients and 9.5% of PBT recipients developed HLA antibodies after BT.Phenotypic and functional analyses were performed in pre-BT, 2 weeks post-BT, and more than 10 weeks post-BT samples (PBT: n=10; DST: n=14).

RESULT: The number of donor-reactive interferon-γ-producing memory T cells increased 2 weeks post-BT, but only in the DST group, increased frequencies persisted beyond 10 weeks (P0.004). In the DST recipients, the proportion of natural killer cells (CD3(-)CD56(+)) significantly increased after BT (P=0.01), whereas in PBT recipients, the proportion of regulatoryT cells (CD4(+)CD25(+)Foxp3(+)CD127 low) significantly increased at 2 weeks post-BT (P=0.039). Microarray analysis confirmed increased activity of genes involved in function of natural killer cells,Tcells, and Bcells in DSTrecipients and increased expression of immune regulatory genes (galectin-1, Foxo3a, and follistatin-like 3) in PBT recipients. Galectin-1 expression by quantitative polymerase chain reaction was significantly enhanced in peripheral blood cells after PBT (P0.05).

CONCLUSION: Decreased immune effector mechanisms combined with an increased immune regulatory cell signature after HLA-DR-matched BT in nonsensitized patients is in line with clinical observations of improved outcome of a subsequent graft. Previous sensitization, however, may lead to HLA antibody formation and prolonged donor-specific memory T-cell reactivity after BT.

Medienart:

E-Artikel

Erscheinungsjahr:

2010

Erschienen:

2010

Enthalten in:

Zur Gesamtaufnahme - volume:90

Enthalten in:

Transplantation - 90(2010), 11 vom: 15. Dez., Seite 1192-9

Sprache:

Englisch

Beteiligte Personen:

Eikmans, Michael [VerfasserIn]
Waanders, Marloes M [VerfasserIn]
Roelen, Dave L [VerfasserIn]
van Miert, Paula P M C [VerfasserIn]
Anholts, Jacqy D H [VerfasserIn]
de Fijter, Hans W [VerfasserIn]
Brand, Anneke [VerfasserIn]
Claas, Frans H J [VerfasserIn]

Themen:

82115-62-6
CD3 Complex
CD56 Antigen
FOXP3 protein, human
Forkhead Transcription Factors
HLA Antigens
IL2RA protein, human
Interferon-gamma
Interleukin-2 Receptor alpha Subunit
Interleukin-7 Receptor alpha Subunit
Isoantibodies
Journal Article
NCAM1 protein, human

Anmerkungen:

Date Completed 07.01.2011

Date Revised 10.03.2022

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM204426685