RRC ID 50042
Author Ueta H, Kitazawa Y, Sawanobori Y, Ueno T, Ueha S, Matsushima K, Matsuno K.
Title Single blood transfusion induces the production of donor-specific alloantibodies and regulatory T cells mainly in the spleen.
Journal Int Immunol
Abstract Donor-specific blood transfusion is known to induce alloresponses and lead to immunosuppression. We examined their underlying mechanisms by employing fully allogeneic rat combinations. Transfused recipients efficiently produced alloantibodies of the IgM and IgG subclasses directed against donor class I MHC. The recipients exhibited active expansion of CD4+ T cells and CD4+FOXP3+ regulatory T cells (Treg cells), followed by CD45R+ B cells and IgM+ or IgG subclass+ antibody-forming cells mainly in the spleen. From 1.5 days, the resident MHCII+CD103+ dendritic cells (DCs) in the splenic T-cell area, periarterial lymphocyte sheath, formed clusters with recipient BrdU+ or 5-ethynyl-2'-deoxyuridine+ cells, from which the proliferative response of CD4+ T cells originated peaking at 3-4 days. Transfusion-induced antibodies had donor passenger cell-depleting activity in vitro and in vivo and could suppress acute GvH disease caused by donor T cells. Furthermore, Treg cells significantly suppressed mixed leukocyte reactions in a donor-specific manner. In conclusion, single blood transfusion efficiently induced a helper T-cell-dependent anti-donor class I MHC antibody-forming cell response with immunoglobulin class switching, and a donor-specific Treg cell response mainly in the spleen, probably by way of the indirect allorecognition via resident DCs. These antibodies and Treg cells may be involved, at least partly, in the donor-specific transfusion-induced suppression of allograft rejection.
Volume 30(2)
Pages 53-67
Published 2018-3-8
DOI 10.1093/intimm/dxx078
PII 4816104
PMID 29361165
PMC PMC5892146
MeSH Animals Antibody Formation / immunology* Antigens Blood Donors Blood Transfusion* Cell Communication / immunology Complement System Proteins / immunology Cytotoxicity, Immunologic Dendritic Cells / immunology Dendritic Cells / metabolism Epitopes, T-Lymphocyte / immunology Epitopes, T-Lymphocyte / metabolism Graft vs Host Disease / etiology Immunity Immunohistochemistry Immunosuppression Therapy Isoantibodies / blood Isoantibodies / immunology* Lymphocyte Culture Test, Mixed Lymphocyte Depletion Rats Spleen / immunology* T-Lymphocytes, Regulatory / immunology* T-Lymphocytes, Regulatory / metabolism
IF 3.519
Times Cited 2
Rats ACI/NKyo (StrainID=6)