Cell Differentiation

Lhasa Proteins Try, but Only T-bet Matters

Science's STKE  21 Mar 2000:
Vol. 2000, Issue 24, pp. tw11
DOI: 10.1126/stke.2000.24.tw11

Naïve T helper lymphocytic cells differentiate into Th1 and Th2 cells, and they are defined by the cytokines they produce. The transcription factors GATA-3 and c-Maf are important for Th2 differentiation, but the components that cause Th1 differentiation are less well defined. Szabo et al. have identified a protein, T-bet (T box expressed in T cells), that directs the differentiation of T helper cells into the Th1 subtype. T-bet expression was observed in Th1 but not Th2 cells, and expression of T-bet was increased after engagement of the T cell receptor. The authors found that T-bet strongly increased interferon (IFN) gamma expression, a marker for Th1 differentiation. Also, forced expression of T-bet in Th2 cells considered to be completely differentiated redirected the Th2 cells into the Th1 phenotype, as measured by decreases in interleukin (IL)-5 and IL-4 production. However, the decrease in IL-5 production was much more pronounced than the decrease in IL-4 production. Although IL-5 expression is very much dependent on the transcriptional activity of GATA-3, IL-4 expression depends on the concerted activity of several transcription factors including GATA-3. Thus, the authors speculate that one function of T-bet may be to directly inhibit GATA-3 activity and to redirect differentiation to the Th1 pathway.

Szabo, S.J., Kim, S.T., Costa, G.L., Zhang, X., Garrison Fathman, C., and Glimcher, L.H. (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669. [Online Journal]