Expression of complement regulatory proteins on human natural killer cell subsets.
The cell surface complement regulatory (CReg) proteins CD46, CD55 and CD59 are widely distributed on human leucocytes and protect against complement-mediated damage. To investigate heterogeneity in CReg protein expression by human natural killer (NK) cells, levels were assessed on resting and activated NK cell subsets identified phenotypically on the basis of expression of CD56 and CD158 markers. Levels of all three CReg proteins on CD56+ cells were lower than on T cells (p<0.05). Freshly isolated CD56(bright) cells expressed higher levels of CD55 than CD56dim cells (p<0.05). CD158a+ cells expressed significantly lower levels of both CD46 and CD59, and CD158e+ cells expressed significantly lower levels of CD46, than CD158a(-) CD158e(-) cells, respectively (both p<0.05). Stimulation with PHA did not significantly alter NK cell surface CReg protein levels whereas, following culture with IL-2, CD46 and CD59 were decreased on both CD56bright and CD56dim subsets (p<0.05). In the case of CD59, this was independent of T cells. Only CD46 was significantly downregulated on CD158b+ (GL183+) and CD158e (NKB1+) subsets (p<0.05). However, culture in IL-15 significantly increased levels of all three CReg proteins. These observations that CReg proteins are downregulated on certain NK cell subsets following activation with IL-2 are opposite to previous findings for other leucocyte subpopulations. Activated NK cells may instead use other strategies for protection against complement-mediated damage in a local inflammatory response.
Wang
Lin
L
Division of Immunology, School of Infection and Host Defence, University of Liverpool, Liverpool, UK.
Halliday
Deborah
D
Johnson
Peter M
PM
Christmas
Stephen E
SE
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D018958:CD55 Antigens / Q000032:analysis; D018957:CD59 Antigens / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis* / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051916:Membrane Cofactor Protein / Q000032:analysis; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D054342:Receptors, KIR2DL1 / Q000032:analysis; D054344:Receptors, KIR2DL3 / Q000032:analysis; D054341:Receptors, KIR3DL1 / Q000032:analysis
D000945:Antigens, Differentiation, T-Lymphocyte; D018958:CD55 Antigens; D018957:CD59 Antigens; D019409:Interleukin-15; D007376:Interleukin-2; D051916:Membrane Cofactor Protein; D010835:Phytohemagglutinins; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1; D003165:Complement System Proteins