Release of surface-expressed lactoferrin from polymorphonuclear neutrophils after contact with CD4+ T cells and its modulation on Th1/Th2 cytokine production.

It is conceivable that a membrane component(s) is transferred from antigen-presenting cells to T cells after antigenic stimulation. However, it is not clear whether a certain membrane component(s) is transferred from polymorphonuclear neturophils (PMN) to T cells for immunomodulation. In the presence study, we cocultured two of the three autologous cells-PMN, CD4+ T, and red blood cells (RBC)-homotypically or heterotypically for 1 h. Spontaneous membrane exchange between autologous PMN-PMN and PMN-CD4+ T but not between CD4+ T-CD4+ T or RBC-CD4+ T was observed with a confocal microscope. Loss of membrane exchange between two paraformaldehyde-fixed cells suggests that mutual membrane exchange is via cell-cell contact. Different combinations of cellular enzyme-linked immunosorbent assay for measuring the binding between fixed cells and biotinylated cell lysates showed the same tendency. To identify the molecule(s) mediating PMN-CD4+ T binding, we compared the banding of biotinylated PMN lysates and the banding of plain PMN lysate probed by biotinylated CD4+ T lysate in 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We found that a 75- to 80-kDa surface-expressed molecule on PMN exists constantly to mediate PMN-CD4+ T binding. Peptide analysis disclosed that the molecule had 99.8% identity with lactoferrin (LF). The expression of LF on system lupus erythematosis (SLE)-PMN is less than normal PMN. PMN-CD4+ T coculture increased LF expression on CD4+ T. Normal PMN and human milk-derived LF suppressed interferon-gamma (IFN-gamma) but enhanced interleukin (IL)-10 production of anti-CD3+anti-CD28-activated, normal CD4+ T. In contrast, coculture of SLE-PMN and autologous CD4+ T suppressed IFN-gamma and IL-10 production. These results suggest that the surface-expressed LF released from PMN after contact with autologous CD4+ T modulated its T helper cell type 1 (Th1)/Th2 cytokine production. Decreased LF expression on SLE-PMN abnormally modulates Th1/Th2 production by CD4+ T cells.