Therapeutic implications of NK cell regulation of allogeneic CD8 T cell-mediated immune responses stimulated through the direct pathway of antigen presentation in transplantation.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_801325B842D8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Therapeutic implications of NK cell regulation of allogeneic CD8 T cell-mediated immune responses stimulated through the direct pathway of antigen presentation in transplantation.
Journal
mAbs
Author(s)
Rodriguez-Barbosa J.I., Ferreras M.C., Buhler L., Jones N.D., Schneider P., Perez-Simon J.A., Del Rio M.L.
ISSN
1942-0870 (Electronic)
ISSN-L
1942-0862
Publication state
Published
Issued date
10/2018
Peer-reviewed
Oui
Volume
10
Number
7
Pages
1030-1044
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Natural killer (NK) cells are a population of innate type I lymphoid cells essential for early anti-viral responses and are known to modulate the course of humoral and cellular-mediated T cell responses. We assessed the role of NK cells in allogeneic CD8 T cell-mediated responses in an immunocompetent mouse model across an MHC class I histocompatibility barrier to determine its impact in therapeutic clinical interventions with polyclonal or monoclonal antibodies (mAbs) targeting lymphoid cells in transplantation. The administration of an NK cell depleting antibody to either CD8 T cell replete or CD8 T cell-depleted naïve C57BL/6 immunocompetent mice accelerated graft rejection. This accelerated rejection response was associated with an in vivo increased cytotoxic activity of CD8 T cells against bm1 allogeneic hematopoietic cells and bm1 skin allografts. These findings show that NK cells were implicated in the control host anti-donor cytotoxic responses, likely by competing for common cell growth factors in both CD8 T cell replete and CD8 T cell-depleted mice, the latter reconstituting in response to lymphopenia. Our data calls for precaution in solid organ transplantation under tolerogenic protocols involving extensive depletion of lymphocytes. These pharmacological biologics with depleting properties over NK cells may accelerate graft rejection and promote aggressive CD8 T cell cytotoxic alloresponses refractory to current immunosuppression.
Keywords
Animals, Antigen Presentation, CD8-Positive T-Lymphocytes/immunology, Cells, Cultured, Cytotoxicity, Immunologic, Graft Rejection/immunology, Histocompatibility Antigens Class I/genetics, Histocompatibility Antigens Class I/immunology, Humans, Isoantigens/immunology, Killer Cells, Natural/immunology, Lymphocyte Depletion, Mice, Mice, Inbred C57BL, Mutation/genetics, Skin Transplantation, CD8 T cells, MHC class I skin graft, NK cells, bm1, graft rejection, transplantation
Pubmed
Web of science
Open Access
Yes
Create date
31/07/2018 11:07
Last modification date
20/08/2019 15:40
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