The TCR a enhancer (Ea) has served as a paradigm for studying how enhancers organize trans-activators into nucleo-protein complexes thought to recruit and synergistically stimulate the transcriptional machinery. Little is known, however, of either the extent or dynamics of Ea occupancy by nuclear factors during T cell development. Using dimethyl sulfate (DMS) in vivo footprinting, we demonstrate extensive Ea occupancy, encompassing both previously identi®ed and novel sites, not only in T cells representing a developmental stage where Ea is known to be active (CD4 + CD8 + ±DP cells), but surprisingly, also in cells at an earlier developmental stage where Ea is not active (CD4 ± CD8 ± ±DN cells). Partial occupancy was also established in B-lymphoid but not non-lymphoid cells. In vivo DNase I footprinting, however, implied developmentally induced changes in nucleo-protein complex topography. Stage-speci®c differences in factor composition at Ea sequences were also suggested by EMSA analysis. These results, which indicate that alterations in the structure of a pre-assembled nucleo-protein complex correlate with the onset of Ea activity, may exemplify one mechanism by which enhancers can rapidly respond to incoming stimuli.

Dengue virus was the first microorganism that was shown to induce generation of antigen-specific suppressor T (TS) cells in mice. The cascade of the three generations of TS cells (TS1, TS2, TS3) and their secretary products, the suppressor factors (SF1, SF2), was delineated. The TS pathway was proposed to be protective through inhibition of the production of enhancing antibody, which may enhance the severity of dengue disease. The currently second most favoured mechanism of severe dengue disease is the 'cytokine tsunami'. During the last decade, suppressor/regulatory T cells have been studied in greater detail using modern techniques in various diseases, including viral infections. This brief review discusses the role of dengue-specific suppressor T cells in protection and/or induction of severe dengue disease in view of our current understanding of suppressor/regulatory T cells.

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