serval:BIB_801325B842D8
Therapeutic implications of NK cell regulation of allogeneic CD8 T cell-mediated immune responses stimulated through the direct pathway of antigen presentation in transplantation.
10.1080/19420862.2018.1502127
000445653300009
30036156
Rodriguez-Barbosa
J.I.
author
Ferreras
M.C.
author
Buhler
L.
author
Jones
N.D.
author
Schneider
P.
author
Perez-Simon
J.A.
author
Del Rio
M.L.
author
article
2018-10
mAbs
1942-0870
1942-0862
journal
10
7
1030-1044
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.
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
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
University of Lausanne
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