title: Characterizing a soluble survival signal for activated lymphocytes from CD14+ cells.
abstract: T-cell activation requires at least two signals: antigen and a costimulatory signal. As antigen-presenting cells play an important role in this area, the role of CD14+ cells in T-cell activation, proliferation and activation-induced cell death (AICD) was investigated. Using phytohaemagglutinin (PHA) activation, it was found that CD14+ cell depletion resulted in significantly greater AICD, decreased lymphocyte growth and up-regulated interleukin-2 (IL-2) secretion. However, T-cell activation was delayed according to the expression of CD69 and CD25. Dynabeads conjugated with anti-CD14 monoclonal antibody (mAb) bound CD14+ cells and induced secretion of IL-1beta, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and IL-6, but not IL-2, IL-12 or IL-15. Supernatants were collected from Dynabeads-activated CD14+ cell cultures and designated as 'CD14 cocktails'. Addition of CD14 cocktails to CD14+ cell-depleted mononuclear cell cultures reversed the increased AICD, decreased lymphocyte growth and increased IL-2 secretion. Depletion of IL-1beta and TNF-alpha in the CD14 cocktails by panning followed by blocking with the corresponding mAbs had no effect on the active AICD protection. TGF-beta was determined not to be the active factor owing to the presence of >1.0 ng of TGF-beta in the media for culturing both CD14+ and CD14- peripheral blood mononuclear cells (PBMC). The CD14 cocktails did not contain IL-12 and IL-15. Depletion of IL-6 with panning followed by blocking residual IL-6 with anti-IL-6 mAb significantly reduced the protective effect of the CD14 cocktails. Human recombinant IL-6 also partially reversed the effects of CD14+ cell depletion on AICD, lymphocyte growth and IL-2 secretion. The data suggest that IL-6 is one of the active factors in the survival signal from CD14+ cells.
authors.affiliation: The Department of Microbiology and Immunology, the Arizona Arthritis Center, the University of Arizona, Tucson, Arizona, USA. x.l.tang@cheerful.com
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Tang
authors.forename: David E
authors.initials: DE
authors.lastname: Yocum
authors.forename: David
authors.initials: D
authors.lastname: DeJonghe
authors.forename: Kathy
authors.initials: K
authors.lastname: Nordensson
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D010835:Phytohemagglutinins; C028784:phytohemagglutinin-P