Chemoattractant activity of IL-2 for human lymphocytes: a requirement for the IL-2 receptor beta-chain.
Recombinant human interleukin-2 (IL-2) stimulated locomotion and chemotaxis of human blood lymphocytes as measured by shape change to a polar morphology, by orientation in a chemotactic gradient, and by a collagen gel invasion assays. IL-2 stimulated locomotion of a larger number of lymphocytes than IL-8 or macrophage inflammatory protein (MIP)-1 alpha, but the maximally effective concentration of all three was similar (around 100 ng/ml). Activation of the lymphocytes by culture for 24-48 hr in fetal calf serum (FCS), anti-CD3, or purified protein derivative (PPD) increased the proportion of responsive cells, though even direct from blood, > 20% of lymphocytes showed locomotor responses to IL-2, a figure which was similar to the number of IL-2 receptor (IL-2R) beta+ lymphocytes but higher than the number of IL-2R alpha+ cells. The effect of antibodies to IL-2R alpha and IL-2R beta as inhibitors of these responses was therefore tested. Anti-IL-2R beta (alpha IL-2R beta) completely inhibited the response of both resting and activated cells: alpha IL-2R alpha had no inhibitory effect on the locomotion of lymphocytes direct from blood, and only partially inhibited locomotion after culture for 48 hr in alpha CD3 or PPD. The locomotor response to IL-2 was inhibited by pretreatment of the cells with herbimycin, a protein tyrosine kinase (PTK) inhibitor, an observation consistent with PTK control of cytoskeletal activity following binding of IL-2 to IL-2R beta. These results suggest that the beta-chain of the IL-2R is required for activation of lymphocyte locomotion by IL-2 and that binding of IL-2 to this chain alone is sufficient for a response.
Wilkinson
P C
PC
Immunology Department, University of Glasgow, U.K.
Newman
I
I
D016227:Benzoquinones; D002478:Cells, Cultured; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D003094:Collagen; D016207:Cytokines / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005782:Gels; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D047029:Lactams, Macrocyclic; D016131:Lymphocyte Subsets / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D017828:Rifabutin / Q000031:analogs & derivatives; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016227:Benzoquinones; D054407:Chemokine CCL4; D016207:Cytokines; D005782:Gels; D007376:Interleukin-2; D047029:Lactams, Macrocyclic; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011809:Quinones; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D017828:Rifabutin; C020754:herbimycin; D003094:Collagen; D011505:Protein-Tyrosine Kinases