IFN-alpha acts on T-cell receptor-triggered human peripheral leukocytes to up-regulate CCR5 expression on CD4+ and CD8+ T cells.
Interleukin-12 (IL-12) as well as IL-2 was recently shown to up-regulate CCR5 expression on T-cell receptor (TCR)-triggered human T cells. Because of the functional similarity between interferon-alpha (IFN-alpha) and IL-12, the present study investigated whether IFN-alpha also up-regulates T cell CCR5 expression. CCR5 was marginally detected on T cells from unstimulated human peripheral blood leukocytes (PBLs) and only slightly induced on PBL T cells following stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies (mAbs). When anti-CD3/anti-CD28-triggered PBLs were exposed to IFN-alpha, T cells expressed high levels of CCR5. The levels of CCR5 expression were comparable to those induced by IL-12. However, when purified T cells instead of unfractionated PBL were stimulated with anti-CD3/CD28 and then exposed to IL-12 or IFN-alpha, CCR5 expression was induced by IL-12 but not by IFN-alpha. IFN-alpha was found to act on anti-CD3/anti-CD28-stimulated PBL to promote their IL-12 production. Moreover, addition of anti-IL-12 mAb to IFN-alpha-stimulated cultures of anti-CD3/CD28-pretreated PBL resulted in considerable inhibition of CCR5 expression. Together, these results indicate that IFN-alpha as well as IL-12 up-regulates CCR5 expression on TCR-triggered T cells and that IFN-alpha functions not by acting directly on T cells but via enhancing IL-12 production by PBL.
Yang
Y F
YF
Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Japan.
Tomura
M
M
Iwasaki
M
M
Ono
S
S
Zou
J P
JP
Uno
K
K
Shearer
G M
GM
Fujiwara
H
H
Hamaoka
T
T
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D015854:Up-Regulation
D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D019713:Receptors, CCR5; D018664:Interleukin-12