Activation of T cells by antigen-presenting cells requires the formation of an immunological synapse, which involves changes in membrane dynamics and cell polarity within the first few hours of contact, and the generation of secondary messengers that trigger cytokine production and T-cell effector functions. Now, Chan and colleagues describe a previously unrecognized late phase of cell polarity in some CD4+ T cells that is controlled by CRTAM (MHC-class-I-restricted T-cell-associated molecule) and that regulates interferon-γ (IFNγ) and interleukin-22 (IL-22) production.

CRTAM is an immunoglobulin-superfamily transmembrane protein that contains a PDZ domain, indicating that it might be capable of assembling protein complexes at the cell membrane. Here, the authors showed that CRTAM is transiently expressed, between 6 and 24 hours following T-cell receptor (TCR) ligation, on the surface of∼ 10–40% of naive CD4+ T cells. Compared with wild-type cells, CRTAM-deficient CD4+ T cells produced lower levels of IFNγ and IL-22 (and to a lesser extent IL-17), but similar levels of IL-4, and had a higher rate of proliferation following activation.