Interleukin 10 regulates cell surface and soluble LIR‐2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro

Dendritic cells (DC) are unique in their ability to stimulate naive T cells to proliferate and to differentiate into effector T cells. DC, however, can also inhibit T cell activation and play a role in central and peripheral tolerance. IL‐10 has been shown to render DC tolerogenic by unknown mechanisms. Using a combined monoclonal antibody/retroviral expression cloning approach, we show here that the inhibitory receptor LIR‐2 (leukocyte immunoglobulin‐like receptor‐2, CD85d) is specifically up‐regulated by IL‐10 on maturing human DC. LPS‐stimulated, LIR‐2‐transfected DC inhibited the proliferation of T cells in autologous, as well as allogeneic culture systems in vitro. In addition, overexpression of LIR‐2 on resting T cells, which lack LIR‐2 expression, inhibited T cell proliferation induced by TCR activation. A novel soluble form of LIR‐2 was detected in culture supernatants of maturing DC. IL‐10 treatment of DC potently inhibited the production of soluble LIR‐2. Recombinant soluble LIR‐2 was able to completely restore the proliferation of T cells activated with LPS‐plus IL‐10‐treated DC. Thus, IL‐10 renders DC hypostimulatory by up‐regulating cell surface LIR‐2 and by inhibiting soluble LIR‐2 in vitro.