Cord blood and adult T cells show different responses to C1q-bearing immune complexes

Abstract

We have previously shown that T cells can be activated through cell-surface C1q receptors, resulting in secretion of interferon-γ (IFN-γ) and tumor necrosis factor α (TNFα), further demonstrating the intimate linkage between innate and adaptive immunity. In this current report, we sought to determine whether: (1) T cell responses to C1q-bearing immune complexes are dependent on the maturational status of the T cells and (2) whether signaling through the C1q receptor on T cells modulates conventional activation mediated through the conventional T cell receptor (TCR)/CD3 signaling complex. We first examined the capacity of neonatal T cells to respond to C1q-bearing immune complexes using IFNγ, IL-2, and MIF secretion as measures of activation (MIF was chosen because of its crucial role in coordinating innate and adaptive immunity). Neonatal T cells produced significantly less IFNγ but not IL-2, when stimulated by C1q immune complexes compared with adult T cells. MIF levels did not exceed background levels in these experiments. Next, we examined the capacity of C1q-bearing immune complexes to regulate signaling through the conventional TCR/CD3 signaling complex. Pre-incubating adult T cells with C1q-bearing immune complexes significantly reduced IFNγ secretion when those same cells were subsequently stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. Pre-incubation of neonatal T-cells with C1q-bearing immune complexes had no effect on IFNγ secretion, although IFNγ secretion was lower than that found in adult T cells for each experimental condition. We speculate that reduced IFNγ secretion after pre-incubation with C1q immune complexes may be due to IL-10 secretion, which was observed in C1q-stimulated adult (but not neonatal) T cells. Conclusions: C1q-bearing immune complexes exert complex effects on mature T cells that include both pro- and anti-inflammatory responses. Immunologic maturation is required for these effects, as cord blood T cells are relatively hyporesponsive to C1q-bearing immune complexes compared with adult T cells.