Cell-cell cooperation at the T helper cell/mast cell immunological synapse

Abstract

It has been suggested that mast cells might serve, under certain circumstances, as antigen-presenting cells (APCs) for T cells. However, whether cognate interactions between mast cells and class II-restricted CD4+ T cells actually occur is still an open question. We addressed this question by using peritoneal cell-derived mast cells (PCMCs) and freshly isolated peritoneal mast cells as APC models. Our results show that in vitro treatment of PCMCs with interferon-γ and interleukin-4 induced surface expression of mature major histocompatibility complex class II molecules and CD86. When interferon-γ/interleukin-4-primed PCMCs were used as APCs for CD4 + T cells, they induced activation of effector T cells but not of their naive counterparts as evidenced by CD69 up-regulation, proliferation, and cytokine production. Confocal laser scanning microscopy showed that CD4 + T cells formed immunological synapses and polarized their secretory machinery toward both antigen-loaded PCMCs and freshly isolated peritoneal mast cells. Finally, on cognate interaction with CD4+ T cells, mast cells lowered their threshold of activation via Fc∈RI. Our results show that mast cells can establish cognate interactions with class II-restricted helper T cells, implying that they can actually serve as resident APCs in inflamed tissues. © 2009 by The American Society of Hematology.