Molecular interaction between CD58 and CD2 counter-receptors mediates the ability of monocytes to augment T cell activation by IL-12

Abstract

IL-12 stimulates both T and NK cells and is pivotal in the development of the Th1 immune response. In this work, we show that an interaction between CD2 and CD58 on activated T cells and monocytes, respectively, regulates the T cell response to IL-12. B cells provide little IL-12-specific costimulation, and this correlates with the low level of CD58 on B cells relative to monocytes and the lack of significant up-regulation in response to IFN-gamma or PHA activation. CHO cell transfectants expressing CD58 at a level comparable with that found on monocytes restore IL-12 responsiveness to APC-depleted T cells. This effect is not observed with CHO cells expressing CD48, a second CD2 ligand with a low avidity for CD2 relative to CD58. Thus, in addition to augmenting adhesion between T cells and their cognate APCs and facilitating TCR-triggered activation, the CD2-CD58 interaction uniquely optimizes the T cell response to IL-12.