title: Selective activation of peripheral blood T cell subsets by endotoxin infusion in healthy human subjects corresponds to differential chemokine activation.
abstract: 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.
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, NY 14627, USA.
authors.forename: Asit K
authors.initials: AK
authors.lastname: De
authors.forename: Carol L
authors.initials: CL
authors.lastname: Miller-Graziano
authors.forename: Steve E
authors.initials: SE
authors.lastname: Calvano
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Laudanski
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Lowry
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
authors.forename: Natasa
authors.initials: N
authors.lastname: Rajicic
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000097:blood / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D018655:Lymphocyte Count; D008297:Male; D019707:Receptors, Chemokine / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine