To examine the cell dynamics of an immune response, the researchers used laser scanning microscopy to take 3D snapshots of T cells in the spleen during infection. The authors infected mice with Listeria monocytogenes that expressed a well-studied antigen, ovalbumin. They then examined the animals' spleens at different times, staining for T cells (of the CD8+ T cell subtype) that could recognize and kill cells expressing ovalbumin antigens.
Immune responses can be initiated in the spleen, which is subdivided into compartments containing different kinds of immune cells; upon infection, the authors saw increased movements of T cells between certain compartments. Initiation of the immune response in the spleen appeared to take place within the lymphocyte-containing white pulp, at the border between B cell–rich areas and a T cell–rich area known as PALS. What is so special about this zone that drives the immune response will have to be addressed in future studies.
Later during infection, T cells moved between the white pulp and red blood cell–rich red pulp areas of the spleen via structures called bridging channels. Only once they made it to the red pulp did the T cells have access to the circulation and travel to the rest of the body to fight infection.
After infection was resolved, memory T cells (those that had seen the antigen) were found in both the red pulp and B cell areas of the spleen. When animals were challenged with a second infection, memory T cells moved from the B cell area to the PALS and commenced later steps in the response. “For a CD8+ T cell, it was rather bizarre to find them in the B cell areas,” says Lefrançois. “We're still trying to understand the functional significance.”