title: Upregulation of CD4 on CD8+ T cells: CD4dimCD8bright T cells constitute an activated phenotype of CD8+ T cells.
abstract: Aside from an intermediate stage in thymic T-cell development, the expression of CD4 and CD8 is generally thought to be mutually exclusive, associated with helper or cytotoxic T-cell functions, respectively. Stimulation of CD8+ T cells, however, induces the de novo expression of CD4. We demonstrate that while superantigen (staphylococcal enterotoxin B, SEB) and anti-CD3/CD28 costimulation of purified CD8+ T cells induced the expression of CD4 on CD8+ T cells by 30 and 17%, respectively, phytohaemagglutinin (PHA) stimulation did not induce CD4 expression on purified CD8+ T cells but significantly induced the expression of both CD4 on CD8 (CD4dimCD8bright) and CD8 on CD4 (CD4brightCD8dim) T cells in unfractionated peripheral blood mononuclear cells (PBMC). The level of the PHA-mediated induction of CD4dimCD8bright and CD4brightCD8dim was at 27 and 17%, respectively. Depletion of CD4+ T cells from PBMC abrogated this PHA-mediated effect. Autologous CD4+ and CD8+ T-cell co-cultures in the presence of PHA induced this CD4dimCD8bright T-cell expression by 33%, demonstrating a role for CD4 cells in the PHA-mediated induction of the double positive cells. The induction of CD4dimCD8bright was independent of a soluble factor(s). Phenotypic analysis of CD4dimCD8bright T cells indicated significantly higher levels of CD95, CD25, CD38, CD69, CD28, and CD45RO expression than their CD8+CD4- counterparts. CD4dimCD8bright T cells were also negative for CD1a expression and were predominantly T-cell receptor (TCR) alphabeta cells. Our data demonstrate that CD4dimCD8bright T cells are an activated phenotype of CD8+ T cells and suggest that CD4 upregulation on CD8+ T cells may function as an additional marker to identify activated CD8+ T cells.
authors.affiliation: Department of Immunology and Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Rush University, Chicago, IL 60612, USA.
authors.forename: Y B
authors.initials: YB
authors.lastname: Sullivan
authors.forename: A L
authors.initials: AL
authors.lastname: Landay
authors.forename: J A
authors.initials: JA
authors.lastname: Zack
authors.forename: S G
authors.initials: SG
authors.lastname: Kitchen
authors.forename: L
authors.initials: L
authors.lastname: Al-Harthi
mesh_terms: D001685:Biological Factors / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D001685:Biological Factors; D017077:Culture Media, Conditioned; D010835:Phytohemagglutinins