Natural killer cell activation in the lung allograft early posttransplantation.
BACKGROUND
In addition to their known antiviral and host defense functions, emerging evidence suggests that natural killer (NK) cells may influence allograft outcomes after solid organ transplantation. Although it is accepted that NK cells are activated in the absence of self-major histocompatibility complex (MHC) class I molecules, little is known of how NK cell dynamics change after transplantation of a MHC disparate lung allograft.


METHODS
To assess this, we characterized longitudinal changes in NK cell frequency and phenotype, using flow cytometry, both in the peripheral blood and lung allograft in 34 patients undergoing lung transplantation.


RESULTS
NK cell frequency decreased with time from transplant with mature NK cells being replaced by a population of less differentiated NK cells expressing lower levels of killer cell immunoglobulin-like receptors. In contrast to peripheral blood, NK cells within the allograft consisted of a greater proportion of CD56 cells, expressed less killer cell immunoglobulin-like receptors, and demonstrated an activated phenotype. In clinically stable recipients, peripheral blood NK cells were not activated, however, this contrasted markedly with a small subset of patients experiencing acute allograft rejection or cytomegalovirus reactivation, whose NK cells demonstrated a more activated profile.


CONCLUSIONS
Our studies suggest that NK cells become activated after MHC-mismatched lung transplantation.
Meehan
Aislin C
AC
Department of Medicine, Monash University, Melbourne, Victoria, Australia.
Sullivan
Lucy C
LC
Mifsud
Nicole A
NA
Brooks
Andrew G
AG
Snell
Greg I
GI
Kotsimbos
Tom C
TC
Westall
Glen P
GP
D000208:Acute Disease; D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008137:Longitudinal Studies; D016040:Lung Transplantation / Q000009:adverse effects*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054340:Receptors, KIR / Q000378:metabolism; D013997:Time Factors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D019002:CD56 Antigen; D007166:Immunosuppressive Agents; D008024:Ligands; D054340:Receptors, KIR