title: 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.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Pollok
authors.forename: J
authors.initials: J
authors.lastname: Hurtado
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: H E
authors.initials: HE
authors.lastname: Broxmeyer
authors.forename: B S
authors.initials: BS
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D054407:Chemokine CCL4; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000494:pharmacology*; D018121:Receptors, Cytokine / Q000032:analysis*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D054407:Chemokine CCL4; D016207:Cytokines; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D018121:Receptors, Cytokine