Immunology Ascent on T Cell Control

The T-box family transcription factor, T-bet, has recently been identified as a possible master regulator in T helper 1 (TH1) immune responses through the transactivation of the gene for interferon- (IFN-). Two studies now look at the effect of T-bet deficiencies. Szabo et al. found that the absence of T-bet expression in mice profoundly attenuated production of IFN- by natural killer and CD4⁺ T cells and also shifted the cytokine profile of CD4⁺ T cells toward that of a TH2 phenotype. Surprisingly, IFN- expression by CD8⁺ T cells was not affected. Finotto et al. observed that T-bet-deficient mice develop spontaneous airway inflammation resembling acute and chronic forms of human asthma. T-bet expression is also reduced in airway tissue from asthmatic patients, which suggests that dysregulation of this transcription factor might contribute to airway hyper-responsiveness in humans.

S. J. Szabo, B. M. Sullivan, C. Stemmann, A. R. Satoskar, B. P. Sleckman, L. H. Glimcher, Distinct effects of T-bet in TH1 lineage commitment and IFN- production in CD4 and CD8 T cells. Science 295, 338-342 (2002). [Abstract] [Full Text]

S. Finotto, M. F. Neurath, J. N. Glickman, S. Qin, H. A. Lehr, F. H. Y. Green, K. Ackerman, K. Haley, P. R. Galle, S. J. Szabo, J. M. Drazen, G. T. De Sanctis, Laurie H. Glimcher, Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336-338 (2002). [Abstract] [Full Text]