title: T-cell receptor activation of human CD4(+) T cells shifts the innate TLR response from CXCL8(hi) IFN-γ(null) to CXCL8(lo) IFN-γ(hi).
abstract: Toll-like receptors (TLRs) play a major part in providing innate immunity against pathogenic microorganisms. Recent studies show that these receptors are also expressed on T cells, which are the sentinels of adaptive immunity. Here, we have investigated the regulatory role of the T-cell receptor in the functioning of these innate receptors in T cells. We show that freshly isolated human CD4(+) T cells readily secrete the neutrophil chemoattractant CXCL8 upon activation with the TLR ligands Pam3CSK and flagellin. In contrast, TCR-activated cells secrete considerably less CXCL8 but start producing IFN-γ upon stimulation with TLR agonists in the absence of concomitant TCR engagement. These T cells show increased activation of p38 and JNK MAP-kinases in response to TLR stimulation, and inhibition of p38 abrogates TLR-induced IFN-γ secretion. The shifting of the T-cell innate immune response from CXCL8(hi) IFN-γ(null) in freshly isolated to CXCL8(lo) IFN-γ(hi) in activated T cells is also observed in response to endogenous innate stimulus, IL-1. These results suggest that the innate immune response of human CD4(+) T cells switches from a proinflammatory to an effector type following activation of these cells through the antigen receptor.
authors.affiliation: Hybridoma Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Akhade
authors.affiliation: Hybridoma Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Ayub
authors.initials: A
authors.lastname: Qadri
mesh_terms: D056704:Adaptive Immunity; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005408:Flagellin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology*; D019169:Jurkat Cells; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology
chemical_list: D015704:CD4 Antigens; C508606:CXCL8 protein, human; D007375:Interleukin-1; D016209:Interleukin-8; D008024:Ligands; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D051193:Toll-Like Receptors; D005408:Flagellin; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: CD4+ T cell; CXCL8; IFN-γ; IL-1; TCR; TLR