3-dimensional plots of CD4+ T cell movement in lymph nodes during priming (left) or tolerizing (right) conditions uncover only subtle differences.

Interactions between T cells and APCs may, under certain conditions, lead to T cell tolerance instead of priming. Disruption of the choreographed T cell behavior in the lymph node is one possible explanation for the distinct functional outcomes. This idea was supported by a recent study showing that CD8⁺ T cells failed to form stable interactions with dendritic cells under tolerizing conditions, suggesting that the lack of a prolonged signal from the APC may lead to T cell tolerance.

Zinselmeyer et al. now show, however, that CD4⁺ T cells in lymph nodes of mice fed antigen with or without adjuvant (to induce priming or tolerance) behaved similarly. Under both conditions, naive T cells formed stable clusters with APCs, although the clusters were smaller and shorter-lived under tolerizing conditions. The authors suggest that subtle differences in T cell clustering, and perhaps the quality of the signal delivered by the APC—rather than the complete presence or absence of a stable interaction—may decide the fate of the T cell.

Shakhar and colleagues, reporting in Nature Immunology (doi:10.1038/ni1210), also found only subtle differences in CD4⁺ T cell behavior in priming or tolerizing conditions. They found that stable T–DC interactions were predictive of T cell activation and proliferation, but not tolerance induction. They speculate that late, dynamic T cell-APC interactions that occur after the T cells resume their motion may deliver the fate-deciding signal.