Mitogen stimulation activates different signaling pathways in early- and late-divided T cells as revealed by cDNA microarray analysis.
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.
Li
Yufeng
Y
Graduate School of Biomedical Science, UT Health Science Center at Houston, Houston, TX 77030, USA.
Wong
Kwong-Kwok
KK
Matsueda
Satoko
S
Efferson
Clay L
CL
Chang
David Z
DZ
Ioannides
Constantin G
CG
Tsuda
Naotake
N
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*
D018076:DNA, Complementary; D005456:Fluorescent Dyes; D008934:Mitogens; D010835:Phytohemagglutinins; D019793:Fluorescein