title: Mitogen stimulation activates different signaling pathways in early- and late-divided T cells as revealed by cDNA microarray analysis.
abstract: Mobilization of tumor-reactive CD8+ T cells remains the major challenge of cancer immunotherapy. Knowing how and when the T cell response expands and differentiates after antigen stimulation would make a significant contribution to the development of tumor vaccines. In the current study, we used CFSE-based cell sorting and cDNA microarray to identify the gene expression profile of adjacent generations of T cells after PHA stimulation. Early-divided generations of T cells responded to stimulation by activating cell cycle and surviving gene pathways, while late generations of T cells had more dramatic changes in transcription of cytokine genes. Reconstruction of biochemical pathways, activated in both early and late generations of T cells, also confirmed the impact of division in focal-adhesion kinases. Because most tumors are infiltrated by lymphocytes, our studies indicate a novel approach to identify 'systemic biological responses' of T cells, which could determine the design, and optimization of effective tumor vaccines.
authors.affiliation: Graduate School of Biomedical Science, UT Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.forename: Kwong-Kwok
authors.initials: KK
authors.lastname: Wong
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.forename: Clay L
authors.initials: CL
authors.lastname: Efferson
authors.forename: David Z
authors.initials: DZ
authors.lastname: Chang
authors.forename: Constantin G
authors.initials: CG
authors.lastname: Ioannides
authors.forename: Naotake
authors.initials: N
authors.lastname: Tsuda
mesh_terms: D002455:Cell Division / Q000187:drug effects; D048429:Cell Size; D002478:Cells, Cultured; D018076:DNA, Complementary; D005434:Flow Cytometry; D019793:Fluorescein; D005456:Fluorescent Dyes; D020869:Gene Expression Profiling; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010835:Phytohemagglutinins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D018076:DNA, Complementary; D005456:Fluorescent Dyes; D008934:Mitogens; D010835:Phytohemagglutinins; D019793:Fluorescein