T-cell activation
OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 cells. Rogers, P.R., Song, J., Gramaglia, I., Killeen, N. & Croft, M. Immunity 15, 445?455 (2001)
Optimal T-cell activation occurs when a T cell receives a signal from the T-cell receptor and a signal from a co-stimulatory receptor, for example CD28. CD28 signalling enhances T-cell proliferation, cytokine secretion and expression of anti-apoptotic proteins. This paper provides direct evidence that OX40 acts synergistically and at a later stage than CD28, and promotes T-cell survival by increasing expression of the anti-apopototic molecules Bcl-xL and Bcl-2.
T-cell development
Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage. Zou, Y. et al. Nature Genet. 29, 332?336 (2001)
The development of immature double-positive thymocytes into mature single-positive CD4+ and CD8+ T cells requires the termination of expression of either the CD4 or CD8 co-receptor. The first intron of the CD4 gene contains a silencer element that represses CD4 transcription. Zou et al. used the Cre/loxP system to show that the CD4 silencer is only required at distinct stages of development. Once a cell is committed to the CD8+ lineage, the CD4 locus remains silent even if the silencer element is removed.
T-cell signalling
Deficiency of small GTPase Rac2 affects T cell activation. Yu, H., Leitenberg, D., Li, B. & Flavell, R.A. J. Exp. Med. 194, 915?925 (2001)
Yu et al. investigated the function of Rac2, a haematopoietic-specific Rho GTPase, in T-cell signalling. Rac2−/− T cells responded poorly to T-cell-receptor stimulation, showing reduced proliferation, Ca2+ mobilization and activation of ERK1/2 and p38. Actin polymerization and cap formation were also decreased in these cells in comparison with wild-type cells. These results show that Rac2 mediates both transcriptional and cytoskeletal changes during T-cell activation.
Innate immunity
Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. Kadowaki, N. et al. J. Exp. Med. 194, 863?869 (2001)
Dendritic cells (DCs) can prime naive T cells and direct the development of immune responses. Yong-Jun Liu's group investigated the expression of Toll-like receptors (TLRs) ? which recognize specific molecular patterns on microbial pathogens ? on human DC subsets. The results show that DC subsets express distinct sets of TLRs, supporting the view that DC subsets have evolved to recognize different microbial pathogens.
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In Breif. Nat Rev Immunol 1, 93 (2001). https://doi.org/10.1038/35100571
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DOI: https://doi.org/10.1038/35100571