Macrophage inflammatory protein-1 alpha rapidly modulates its receptors and inhibits the anti-CD3 mAb-mediated proliferation of T lymphocytes.

Abstract

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a member of the intercrine/chemokine family which consists of basic, heparin-binding, small molecular weight proteins. We have previously shown that a T cell line, CTLL-R8, carried high-affinity receptors for MIP-1 alpha and the proliferation of CTLL-R8 cells was inhibited by murine recombinant (mr) MIP-1 alpha. We extended our previous studies to murine resting splenic T lymphocytes to determine whether the inhibition of T cell proliferation is a general property of MIP-1 alpha. The resting splenic T cells carried approximately 680 high-affinity binding sites for mrMIP-1 alpha; more than 90% of the primary T cells carried MIP-1 alpha receptors. When the T cells were stimulated with immobilized anti-CD3 mAb in the presence of accessory cells, the MIP-1 alpha binding was reduced. The lowest binding was obtained 2 h after anti-CD3 mAb stimulation due to the internalization of MIP-1 alpha receptors. mrMIP-1 alpha inhibited the anti-CD3 mAb-mediated proliferation of murine splenic T lymphocytes. The maximum inhibition was obtained when mrMIP-1 alpha was added 30 min before anti-CD3 mAb stimulation. Slight inhibition of T cell proliferation was observed when mrMIP-1 alpha was added at the same time as anti-CD3 mAb stimulation. These results indicate that T lymphocytes are regulated negatively by MIP-1 alpha, which occurs when the T cells are exposed to MIP-1 alpha before activation. The negative effect of MIP-1 alpha seems to be mediated in part by the inhibition of IL-2 production, for there was a reduction in both the IL-2 mRNA levels and the IL-2 activity in supernatants from T cells preincubated with MIP-1 alpha before anti-CD3 mAb stimulation.