Human mast cells costimulate T cells through a CD28‐independent interaction

Mast cells are innate immune cells usually residing in peripheral tissues, where they are likely to activate T‐cell responses. Similar to other myeloid immune cells, mast cells can function as antigen‐presenting cells. However, little is known about the capacity of human mast cells to costimulate CD4+ T cells. Here, we studied the T‐cell stimulatory potential of human mast cells. Peripheral blood derived mast cells were generated and cocultured with isolated CD4+ T cells. In the presence of T‐cell receptor triggering using anti‐CD3, mast cells promoted strong proliferation of T cells, which was two‐ to fivefold stronger than the “T‐cell promoting capacity” of monocytes. The interplay between mast cells and T cells was dependent on cell–cell contact, suggesting that costimulatory molecules on the mast cell surface are responsible for the effect. However, in contrast to monocytes, the T‐cell costimulation by mast cells was independent of the classical costimulatory molecule CD28, or that of OX40L, ICOSL, or LIGHT. Our data show that mast cells can costimulate human CD4+ T cells to induce strong T‐cell proliferation, but that therapies aiming at disrupting the interaction of CD28 and B7 molecules do not inhibit mast cell mediated T‐cell activation. Human mast cells induce strong activation and proliferation of CD4+ T cells in the presence of a TCR stimulus. This costimulation is mediated through cell–cell contact in a CD28‐independent manner.