IL-8 gene expression and production in human peripheral blood lymphocyte subsets.
We have investigated IL-8 mRNA expression and IL-8 production in highly purified subsets of peripheral blood lymphocytes. T cells stimulated with PHA, ionomycin, or PMA alone failed to express IL-8 mRNA. However T cells stimulated with a combination of PMA and ionomycin or PMA and PHA expressed IL-8 mRNA in a PMA dose-dependent manner and maximally after 3 to 6 h of culture. Induction of IL-8 mRNA appeared to be specifically in the CD4+ T cell subset. Surprisingly, however, T cells were not induced to secrete significant levels of IL-8 polypeptide, even in the presence of accessory monocytes. In addition, immunoprecipitation analysis of PMA/ionomycin-treated T cell lysates detected only minor levels of cellular IL-8 Ag thereby suggesting that in T cells, the production of IL-8 was inhibited at the posttranscriptional level. By contrast, CD3- large granular lymphocytes (LGL) were both induced to express IL-8 mRNA and secrete biologically active IL-8 upon specific stimulation with IL-2 and ligand (anti-CD16 mAb) for the NK cell receptor for IgG-Fc (CD16), or upon nonspecific stimulation with PMA. IL-2 and anti-CD16 mAb synergistically induced IL-8 expression in LGL. Other nonactivating LGL-specific mAb did not induce LGL IL-8 secretion. The amount of IL-8 produced by activated LGL was donor variable, but generally 5 to 10 times less than that secreted by monocytes. The ability of LGL to release IL-8 and a large number of other cytokines further supports the hypothesis that LGL may contribute to both inflammatory and immunologic responses.
Smyth
M J
MJ
Laboratory of Experimental Immunology, NCI-FCRDC, Frederick, MD 21702-1201.
Zachariae
C O
CO
Norihisa
Y
Y
Ortaldo
J R
JR
Hishinuma
A
A
Matsushima
K
K
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D015759:Ionomycin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011961:Receptors, Fc / Q000502:physiology; D017452:Receptors, IgG; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007376:Interleukin-2; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate