Cytotoxic activity of natural killer cells lacking killer-inhibitory receptors for self-HLA class I molecules against autologous hematopoietic stem cells in healthy individuals.
Killer-inhibitory receptors (KIR) are receptors for self-HLA class I molecules, which are expressed on natural killer (NK) cells and small subsets of T-lymphocytes. KIR receptors that do not bind to self-HLA class I have been implicated in the pathogenesis of pure red-cell aplasia and other autoimmune diseases. However, NK cells whose inhibitory receptors lack any apparent self-ligand can also be found in healthy individuals. We therefore tested whether these NK cells are capable of exerting cytotoxic activity against autologous CD34(+) hematopoietic precursors. We detected NK cells whose sole inhibitory receptors were CD94/NKG2-A and that had no affinity for autologous HLA-C molecules. In vitro, such cells were able to kill autologous CD34(+) stem cells that expressed MHC class I antigen at a high level in about 50% of the cases of HLA-C group 2 donors. Two individual clones derived from this NK subpopulation were stimulated by autologous HLA-Cw5/6-positive stem cells, but not by allogeneic HLA-Cw7-positive stem cells. Our findings demonstrate the presence of potentially autoreactive natural killer cells in otherwise healthy individuals.
Grau
Roger
R
Department of Hematology, Children's University Hospital, Tuebingen, Germany.
Lang
Karl S
KS
Wernet
Dorothee
D
Lang
Peter
P
Niethammer
Dietrich
D
Pusch
Carsten M
CM
Handgretinger
Rupert
R
D018952:Antigens, CD34 / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic; D015236:HLA-C Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018189:Immunomagnetic Separation; D007694:Killer Cells, Natural / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D054340:Receptors, KIR
D018952:Antigens, CD34; D001324:Autoantigens; D015236:HLA-C Antigens; C037505:HLA-C*05 antigen; C040178:HLA-C*70 antigen; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D054340:Receptors, KIR