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

Z. Zhou, Y. J. Kim, K. Pollok, J. Hurtado, J. K. Lee, H. E. Broxmeyer, B. S. Kwon

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Macrophage inflammatory protein-1α (MIP-1α) 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-1α and the proliferation of CTLL-R8 cells was inhibited by murine recombinant (mr) MIP-1α. 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- 1α. The resting splenic T cells carried approximately 680 high-affinity binding sites for mrMIP-1α; more than 90% of the primary T cells carried MIP-1α receptors. When the T cells were stimulated with immobilized anti- CD3 mAb in the presence of accessory cells, the MIP-1α binding was reduced. The lowest binding was obtained 2 h after anti-CD3 mAb stimulation due to the internalization of MIP-1α receptors. mrMIP-1α inhibited the anti-CD3 mAb- mediated proliferation of murine splenic T lymphocytes. The maximum inhibition was obtained when mrMIP-1α was added 30 min before anti-CD3 mAb stimulation. Slight inhibition of T cell proliferation was observed when mrMIP-1α was added at the same time as anti-CD3 mAb stimulation. These results indicate that T lymphocytes are regulated negatively by MIP-1α, which occurs when the T cells are exposed to MIP-1α before activation. The negative effect of MIP-1α 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-1α before anti-CD3 mAb stimulation.

Original languageEnglish (US)
Pages (from-to)4333-4341
Number of pages9
JournalJournal of Immunology
Volume151
Issue number8
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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