IgG Immune Complexes Inhibit Naïve T Cell Proliferation and Suppress Effector Function in Cytotoxic T Cells

Abstract

Elevated levels of circulating immune complexes are associated with autoimmunity and with worse prognoses in cancer. Here, we examined the effects of well-defined, soluble immune complexes (ICs) on human peripheral T cells. We demonstrate that IgG-ICs inhibit the proliferation and differentiation of a subset of naïve T cells but stimulate the division of another naïve-like T cell subset. Phenotypic analysis by multi-parameter flow cytometry and RNA-Seq were used to characterize the inhibited and stimulated T cells revealing that the inhibited subset presented immature features resembling those of recent thymic emigrants and non-activated naïve T cells, whereas the stimulated subset exhibited transcriptional features indicative of a more differentiated, early memory progenitor with a naïve-like phenotype. Furthermore, we show that while IgG1-ICs do not profoundly inhibit the proliferation of memory T cells, IgG1-ICs suppress the production of granzyme-β and perforin in cytotoxic memory T cells. Our findings reveal how ICs can link humoral immunity and T cell function.

Keywords: Antigen and Antibody Immune Complexes; IgG Immune Complexes (ICs); Naive and memory T cells; T cell Fc Gamma Receptors (FcgR); T cell Fc Receptors; T cell activation proliferation and inhibition; T cell antibody receptors; T cell non-canonical Fc Receptors.