Neutrophils modulate immunostimulatory activity of immature dendritic cells

PAULO MAFFIA; SANDRA ZITTERMANN; LUCILA SCIMONE; NANCY TATEOSIAN; NICOLÁS AMIANO; DIEGO GUERRIERI; JULIETA COSTA; MACARENA REITIER; VERÓNICA GARCÍA; ANDREW ISSEKUTZ; EDUARDO CHULUYAN

Boston, uSA

Congreso; Congreso Americano de Inmunólogos (AAI)-Immunology 2006; 2006

American Association for Immunologists (AAI)

Recently it has been reported that polymorphonuclear leukocytes(PMNs) induce dendritic cell (DC) maturation and instruct DCs to induce Th1-type T cell responses. In the present study we further investigated the interaction between PMNs and DCs. Allogeneic DCs (2x104) decreased T cell (105) proliferation in the presence of syngeneic PMNs (105). The decreased allogeneic lymphoproliferation was also observed when DCs were pretreated with culture supernatant (CS) from unprimed or primed PMNs. This effect was observed with immature DCs, and was not due to apoptosis or changes in the expression of MHC class I and II or costimulatory molecules. However, PMN-CS treated DCs showed a higher amount of intracellular and secreted TGFâ compared to untreated DCs. A blocking TGFâ mAb reversed the decrease in T cell proliferation induced by PMN-CS-treated DCs. Elastase reproduced the effect of PMN-CS on DC allostimulatory ability and DC TGFâ production. The role of elastase was confirmed by testing the effect of PMN-CS from two patients with cyclic neutropenia, a disease due to mutations in the neutrophil elastase gene. These PMN-CSs were unable to increase DC TGFâ production. Thus PMN decreases the allostimulatory ability of DC by elastase via stimulation of TGFâ production.