A ROLE FOR THE ARCHITECTURAL TRANSCRIPTION FACTORS HMGI(Y) IN CYTOKINE GENE-TRANSCRIPTION IN T-CELLS

The ability of CD4(+) T helper (Th) cells to differentiate into two ph enotypes distinguished by their cytokine profile is a major determinan t of the type of immune response elicited by bacterial, viral or paras itic infections. The development of Th1 cells is associated with delay ed-type hypersensitivity and cell-mediated immune responses while Th2 responses are associated with humoral immunity and allergic inflammati on. While these phenotypes exist at the extremes of the immune respons e and are associated with pathological conditions, there is an enormou s plasticity that allows reversibility and the development of a wide a rray of cytokine profiles. There has been considerable interest in det ermining the signals and transcription factors that govern the differe ntial production of the Th1 and Th2 cytokines. There are now several c andidate transcription factors that may play a role in skewing the cyt okine profile in a distinct direction. Because of the plasticity of th e system, these transcription factors must be able to respond to envir onmental signals in a very subtle manner and not simply be on/off swit ches for expression of the cytokine genes. The architectural transcrip tion factor high mobility group (HMG) I(Y) is a modulator of the funct ion of many of the transcription factors that control cytokine gene tr anscription. HMGI(Y) appears to play either a positive or negative rol e depending on the cytokine promoter and its ratio to other transcript ion factors. It is proposed that HMGI(Y) may have a role in regulating the production of cytokines in favour of a given immune response.