Advances in microscopy have allowed the visualization of T-cell behaviour in lymphoid and some peripheral organs during inflammation. However, little is known about how T cells behave in the brain. A study by Hunter and colleagues now reveals that T cells are readily recruited to the brain during Toxoplasma gondii infection and migrate along infection-induced reticular fibres.

To visualize the behaviour of antigen-specific CD8⁺ T cells during T. gondii infection, the authors injected GFP⁺ (green fluorescent protein) OVA (ovalbumin)-specific CD8⁺ T cells (OT-I–GFP⁺ T cells) into mice that were chronically infected with a strain of the parasite that was engineered to express the OVA peptide. Tetramer analysis showed that the population of OT-I–GFP⁺ T cells migrated to the brain of infected mice and greatly expanded, peaking at 3 weeks following transfer. The expansion of the T-cell population was due to cell recruitment rather than proliferation, as antibody-mediated blockade of vascular cell-adhesion molecule 1, which is required for T-cell entry into the brain, decreased the numbers of OT-I–GFP⁺ T cells. The expansion phase was followed by gradual contraction of the T-cell population in the infected brain, which coincided with an increase in parasite burden, suggesting that the T cells cannot sustain their control of parasite growth.

The authors then examined the motility of the OT-I–GFP⁺ T cells that were found in the brain following T. gondii infection. Using multiphoton microscopy, they observed that the increase in the number of these cells during the first 3 weeks of infection correlated with an increase in their velocity and displacement (total distance travelled from the point of origin). The cells showed heterogeneous migratory behaviour, with some being highly motile and others being slow or stationary in clusters. Furthermore, the authors observed second harmonic generation (SHG) structures in the brains of mice infected with T. gondii. These structures, which are also found in other neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, were formed by a densely organized network of reticular fibres with which OT-I–GFP⁺ T cells were closely associated. Specifically, interaction with the reticular network was associated with pro-migratory changes in T-cell morphology, including formation of lamellipodia and elongation of the cells parallel to the fibres.

This study reveals the presence of a reticular network that develops after T. gondii infection and that is proposed to facilitate the migration of T cells into the brain during inflammation. As these structures have been observed in other neuroinflammatory conditions, targeting them might be of therapeutic benefit.

Author: Rachel David - Copyright © 2009 Nature Publishing Group, a division of MacMillan Publishers Limited; used with permission