ACTIVATION OF HUMAN T-CELLS BY MAJOR HISTOCOMPATABILITY COMPLEX CLASS-II EXPRESSING NEUTROPHILS - PROLIFERATION IN THE PRESENCE OF SUPERANTIGEN, BUT NOT TETANUS TOXOID

The primary function of polymorphonuclear neutrophils (PMN) in the imm une response appears to be acute phagocytic clearance of foreign patho gens and release of inflammatory mediators. Consistent with their assu med lack of major histocompatibility complex (MHC) class II expression , PMN have not been considered to play a role in antigen presentation and T-cell activation. However, recent reports have shown that human P MN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating fact or (GMCSF) or interferon-gamma (IFN-gamma). Thus, under appropriate co nditions, PMN could play a significant role in immune regulation, incl uding T-cell activation, In this report, we demonstrate that human cla ss It-expressing PMN can serve as accessory cells in superantigen (SAg )-mediated T-cell activation. This accessory activity for SAg presenta tion was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IF N-gamma, which acted synergistically to induce MHC class II molecules on PMN. Moreover, the level of MHC class II expression and the magnitu de of SAg-induced T-cell responses were found to be highly correlated and distinctly donor dependent, with PMN from some donors repeatedly s howing fivefold higher responses than PMN from other donors. On the ot her hand, culture of PMN with GM-CSF plus IFN-gamma under conditions t hat resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toroid (TT) or for a TT peptide. These results delineate a new pathway for T -cell activation by SAS that may play an important role in the severit y of SAg-induced inflammatory responses. They also identify a donor-sp ecific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma. (C) 1997 by The American Society of Hematology.