MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA RAPIDLY MODULATES ITS RECEPTORS AND INHIBITS THE ANTI-CD-3 MAB-MEDIATED PROLIFERATION OF T-LYMPHOCYTES

Macrophage inflammatory protein-1alpha (MIP-1alpha) 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 ce ll line, CTLL-R8, carried high-affinity receptors for MIP-1alpha and t he proliferation of CTLL-R8 cells was inhibited by murine recombinant (mr) MIP-1alpha. We extended our previous studies to murine resting sp lenic T lymphocytes to determine whether the inhibition of T cell prol iferation is a general property of MIP-1alpha. The resting splenic T c ells carried approximately 680 high-affinity binding sites for mrMIP-1 alpha; more than 90% of the primary T cells carried MIP-1alpha recepto rs. 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-1alpha receptors. mrMIP-1alpha inhibite d the anti-CD3 mAb-mediated proliferation of murine splenic T lymphocy tes. The maximum inhibition was obtained when mrMIP-1alpha was added 3 0 min before anti-CD3 mAb stimulation. Slight inhibition of T cell pro liferation was observed when mrMIP-1alpha was added at the same time a s anti-CD3 mAb stimulation. These results indicate that T lymphocytes are regulated negatively by MIP-1alpha, which occurs when the T cells are exposed to MIP-1alpha before activation. The negative effect of MI P-1alpha seems to be mediated in part by the inhibition of IL-2 produc tion, for there was a reduction in both the IL-2 mRNA levels and the I L-2 activity in supernatants from T cells preincubated with MIP-la bef ore anti-CD3 mAb stimulation.