Selective Activation of Peripheral Blood T Cell Subsets by Endotoxin Infusion in Healthy Human Subjects Corresponds to Differential Chemokine Activation

Although activation of human innate immunity after endotoxin administration is well established, in vivo endotoxin effects on human T cell responses are not well understood. Most naive human T cells do not express receptors for LPS, but can respond to endotoxin-induced mediators such as chemokines....

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Published in:The Journal of immunology (1950) 2005-11, Vol.175 (9), p.6155-6162
Main Authors: De, Asit K, Miller-Graziano, Carol L, Calvano, Steve E, Laudanski, Krzysztof, Lowry, Stephen F, Moldawer, Lyle L, Remick, Daniel G., Jr, Rajicic, Natasa, Schoenfeld, David, Tompkins, Ronald G
Format: Article
Language:English
Subjects:
Adult
Cell Movement - drug effects
Chemokines - blood
Chemokines - physiology
Cytokines - biosynthesis
Female
Humans
Immunity, Innate - drug effects
Lipopolysaccharides - pharmacology
Lymphocyte Activation - drug effects
Lymphocyte Count
Male
Receptors, Chemokine - analysis
T-Lymphocyte Subsets - drug effects
T-Lymphocyte Subsets - immunology
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Summary:Although activation of human innate immunity after endotoxin administration is well established, in vivo endotoxin effects on human T cell responses are not well understood. Most naive human T cells do not express receptors for LPS, but can respond to endotoxin-induced mediators such as chemokines. In this study, we characterized the in vivo response of peripheral human T cell subsets to endotoxin infusion by assessing alterations in isolated T cells expressing different phenotypes, intracellular cytokines, and systemic chemokines concentration, which may influence these indirect T cell responses. Endotoxin administration to healthy subjects produced T cell activation as confirmed by a 20% increase in intracellular IL-2, as well as increased CD28 and IL-2R alpha-chain (CD25) expression. Endotoxin induced indirect activation of T cells was highly selective among the T cell subpopulations. Increased IL-2 production (36.0 +/- 3.7 to 53.2 +/- 4.1) vs decreased IFN-gamma production (33.8 +/- 4.2 to 19.1 +/- 3.2) indicated selective Th1 activation. Th2 produced IL-13 was minimally increased. Differentially altered chemokine receptor expression also indicated selective T cell subset activation and migration. CXCR3+ and CCR5+ expressing Th1 cells were decreased (CXCR3 44.6 +/- 3.2 to 33.3 +/- 4.6 and CCR5 24.8 +/- 2.3 to 12 +/- 1.4), whereas plasma levels of their chemokine ligands IFN-gamma-inducible protein 10 and MIP-1alpha were increased (61.4 +/- 13.9 to 1103.7 +/- 274.5 and 22.8 +/- 6.2 to 55.7 +/- 9.5, respectively). In contrast, CCR4+ and CCR3 (Th2) proportions increased or remained unchanged whereas their ligands, eotaxin and the thymus and activation-regulated chemokine TARC, were unchanged. The data indicate selective activation among Th1 subpopulations, as well as differential Th1/Th2 activation, which is consistent with a selective induction of Th1 and Th2 chemokine ligands.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.175.9.6155