A critical role for IL-12 in CCR5 induction on T cell receptor-triggered mouse CD4(+) and CD8(+) T cells.
Despite increasing evidence for the role of the chemokine system in leukocyte trafficking, the mechanism underlying the induction of chemokine receptors is poorly understood. Here, we investigated how CCR5, a chemokine receptor implicated in T cell migration to inflammatory sites, is induced in the T cell. CCR5 mRNA was hardly detected in resting T cells and marginally induced following T cell receptor (TCR) stimulation. However, TCR-triggered T cells expressed IL-12 receptor, and stimulation with recombinant IL-12 resulted in high levels of CCR5 expression on both CD4(+) and CD8(+) T cells. In contrast, IL-2 failed to up-regulate CCR5 expression. The effect of IL-12 was selective to CCR5 because IL-12 did not up-regulate CXCR3 expression. Surface expression of CCR5 was shown by staining with anti-CCR5 monoclonal antibody. Stimulation of these CCR5-positive T cells with the relevant chemokine MIP-1 alpha elicited Ca(2+) influx, showing that IL-12-induced CCR5 is functional. These results indicate a critical role for IL-12 in the induction of CCR5 on TCR-triggered T cells.
Iwasaki
M
M
Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan.
Mukai
T
T
Gao
P
P
Park
W R
WR
Nakajima
C
C
Tomura
M
M
Fujiwara
H
H
Hamaoka
T
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D054407:Chemokine CCL4; D005455:Fluorescent Antibody Technique; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D019713:Receptors, CCR5; D018664:Interleukin-12; D007371:Interferon-gamma; D002118:Calcium