Type I interferon is the primary regulator of inducible Ly-6C expression on T cells.
Ly-6C has been proposed as a marker of memory CD8+ T cells. Reports have indicated that Ly-6C is upregulated after T cell receptor (TCR) stimulation or exposure to proinflammatory cytokines. This study examined the relative roles of proinflammatory cytokines and TCR engagement in Ly-6C induction. In vitro experiments tested the effects of cytokines on Ly-6C expression and confirmed interferon-alpha (IFN-alpha) as a primary cytokine that induces Ly-6C expression on CD4+ and CD8+ T cells. The amount and duration of Ly-6C expression were examined on T cells after in vivo induction of proinflammatory cytokines (CpG oligodeoxynucleotides [ODN]) or TCR activation (staphylococcal enterotoxin B [SEB]). In vivo, proinflammatory cytokines transiently upregulated Ly-6C on T cells in the absence of TCR stimulation. TCR stimulation by SEB transiently upregulated Ly-6C expression on antigen-specific and antigen-nonspecific T cells but did not cause long-term upregulation of Ly-6C expression in either population. IFN-alpha was confirmed as a primary inducer of Ly-6C in vivo, as CpG ODN were unable to induce Ly-6C expression in IFN-alphaRI(-/-) mice. Thus, inducible Ly-6C expression on CD4+ and CD8+ T cells is largely due to IFN-alpha in the environment and appears not to be directly correlated with the development of T cell memory.
Schlueter
A J
AJ
Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242-1181, USA. annette-schlueter@uiowa.edu
Krieg
A M
AM
de Vries
P
P
Li
X
X
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D007370:Interferon Type I / Q000502:physiology*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
D000950:Antigens, Ly; C408982:CPG-oligonucleotide; D004768:Enterotoxins; D007370:Interferon Type I; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma