Neutrophils Modulate Immunostimulatory Activity Of Immature Dendritic Cells.

PAULO C. MAFFIA, SANDRA E. ZITTERMANN, M. LUCILA SCIMONE, NANCY TATEOSIAN, NICOLÁS AMIANO, DIEGO GUERRIERI, VIVIANA LUTZKY, VERÓNICA E. GARCIA, ANDREW C. ISSEKUTZ AND H. EDUARDO CHULUYAN

Boston, USA

Congreso; Immunology 2006; 2006

The American Association of Immunologists.

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 TGFβ compared to untreated DCs. A blocking TGFβ 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 TGFβ 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 TGFβ production. Thus PMN decreases the allostimulatory ability of DC by elastase via stimulation of TGFβ production. PICT2002 N° 05-11702; PICT2003 N°5-15069; UBACYT 2004-2007, M019