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DNA microarray analysis of the gene expression profiles of naïve versus activated tumor-specific T cells
Xueshu Zhang1, Zhuang Chen, Hui Huang
1Department of Oncology, Research Unit, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon Cancer Center, 20 Campus Drive CM200, Saskatoon, Saskatchewan, Canada S7N 0W0.
Abstract:
T cells are a key element in effective cancer immunity, recognizing MHC-antigen peptide complexes on the surface of antigen presenting cells and translating these signals into cytotoxic effector T cell responses. In this study, we systematically investigated by DNA array analysis the expression profiles of 514 immunologically relevant genes in naïve and SP2/0 tumor-specific activated mouse T cell populations. Our data shows that naïve T cells expressed 37 (i.e., 7.6% of the 514) transcripts with expression level (EL) values of > or =2.0, while the activated T cells expressed 101 such transcripts. The expression levels of 9 (1.75% of 514) of the shared transcripts were equivalent in the two populations of T cells. Ninety-six genes were differently expressed upon T cell activation, with 71 (13.81%) being up-regulated and 25 (4.86%) down-regulated. The list of significantly affected genes includes numerous cytokines and their receptors (e.g., IL-2Ralpha, IL-6Ralpha, IL-7Ralpha, IL-16, IL-17R, TGF-beta), chemokines and chemokine receptors (e.g., RANTES, CCR7, CXCR4), alternate surface proteins (e.g., 4-1BB, GITR, integrins-alphaL and -beta7, L-selectin, CD6, CD45 and EMMPRIN), cytoplasmic signaling intermediates (e,g., GATA-3, 14-3-3-eta, CIS1, SMAD4 and JAK1) and an array of other molecules (e.g., NFkappa-B inducing kinase, LTBP3 and persephin), several of which are associated with Th1 responses, and T cell self-regulation or migration. Taken together, our data contribute to our understanding of the generalized processes that accompany T cell activation and, more specifically, to our understanding of the processes associated with T cell activation during antitumor responses.