Gene microarrays reveal extensive differential gene expression in both CD4(+) and CD8(+) type 1 and type 2 T cells.
An important subdivision of effector T cells can be made based on patterns of cytokine production and functional programs. Type 1 T cells produce IFN-gamma and protect against viral pathogens, whereas type 2 cells produce cytokines such as IL-4 and IL-5 and protect against large extracellular parasites. Both CD4(+) and CD8(+) T cells can be polarized into type 1 or type 2 cytokine-secreting cells, suggesting that both populations play a regulatory role in immune responses. In this study, we used high-density oligonucleotide arrays to produce a comprehensive picture of gene expression in murine CD4(+) Th1 and Th2 cells, as well as CD8(+) type 1 and type 2 T cells. Polarized type 1 and 2 cells transcribed mRNA for an unexpectedly large number of genes, most of which were expressed in a similar fashion between type 1 and type 2 cells. However, >100 differentially expressed genes were identified for both the CD4(+) and CD8(+) type 1 and 2 subsets, many of which have not been associated with T cell polarization. These genes included cytokines, transcription factors, molecules involved in cell migration, as well as genes with unknown function. The program for type 1 or type 2 polarization was similar for CD4(+) and CD8(+) cells, since gene expression patterns were roughly the same. The expression of select genes was confirmed using real-time PCR. The identification of genes associated with T cell polarization may give important insights into functional and phenotypic differences between effector T cell subsets and their role in normal responses and inflammatory disease.
Chtanova
T
T
Garvan Institute of Medical Research, Darlinghurst, Australia.
Kemp
R A
RA
Sutherland
A P
AP
Ronchese
F
F
Mackay
C R
CR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D003199:Computer Systems; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018075:RNA, Complementary / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D007378:Interleukins; D018075:RNA, Complementary; D012333:RNA, Messenger; D007371:Interferon-gamma