Natural killer-dendritic cell interaction in lymphocyte responses in hypersensitivity reactions to betalactams.
BACKGROUND
Betalactams are the commonest cause of allergic reactions mediated by either IgE or T lymphocytes in which innate and adaptive immune systems mediate the earlier stages of immunological responses. One of the links between these systems is related to the interaction between natural killer (NK) and dendritic cells (DC). We have evaluated the role of NK cells and NK-DC interaction in the immunopathological mechanisms of nonimmediate reactions to betalactams.


METHODS
Patients allergic to amoxicillin (AX) (N = 17) and tolerant controls (N = 13) were included. Changes in phenotype (CD69, IFNγ, perforin, and granzyme B) in AX-stimulated NK cells, the cytotoxic activity on mature or immature DC (imDC), and the proliferation and phenotype of NK lymphocytes after culture with AX and DC were determined by flow cytometry.


RESULTS
Amoxicillin induced activation and increases of perforin and granzyme B (P = 0.007 and P = 0.041 respectively) but not IFNγ production in NK cells from patients. In NK subpopulations, AX induced a significant enhancement of perforin and granzyme B in CD56(dim) (P = 0.005 and P = 0.002 respectively) and of IFNγ in CD56(bright) (P = 0.001). The cytotoxic phenotype was demonstrated by an increase of annexin V only in imDC (P < 0.001). Amoxicillin also induced an increased NK proliferation with different patterns, cytotoxic or proinflammatory, depending on the presence of imDC or mature DC, respectively. No differences were observed in NK cells from tolerant controls.


CONCLUSIONS
These data could demonstrate the involvement of NK cells in the immunopathological mechanisms of nonimmediate allergic reactions to AX, showing that both the innate and adaptive immune systems are involved and crosstalk, producing amplification of the harmful effects observed in these drug reactions.
Chaves
P
P
Research Laboratory, Fundacion IMABIS-Carlos Haya Hospital, Málaga, Spain.
Torres
M J
MJ
Aranda
A
A
Lopez
S
S
Canto
G
G
Blanca
M
M
Mayorga
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000009:adverse effects / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D054353:Perforin; D000658:Amoxicillin; D053804:Granzymes