Although it has been known for many years that activated T cells migrate into nonlymphoid sites of inflammation, the magnitude and timing of this migration relative to activation in lymphoid organs was unknown. I think this paper is highly cited because it addresses these issues by describing the number and location of antigen-specific CD4 T cells at various times after immunization, and does so graphically with the technique of whole animal immunohistology. In addition, the paper describes the unexpected finding that the antigen-experienced CD4 T cells that survive in the nonlymphoid organs are the best producers of the anti-microbial lymphokine interferon-gamma. The fact that David Masopust and Leo Lefrancois published similar findings for CD8 T cells in a contemporary paper likely gave both papers immediate credibility.

The findings in the paper relied heavily on whole animal immunohistology. Although this technique had been used by Oldstone and coworkers to identify the organs harboring virus infection, Lee Reinhardt refined the technique to allow resolution of single cells. This technique should be useful for tracking other immune responses, tumor progression, and infectious agents.

The paper is significant because it points out that immunity to infections may take place in nonlymphoid tissues, not the lymphoid organs that immunologists usually focus on.

My laboratory has spent the last 10 years developing systems that allow the direct visualization of CD4 T cells as they participate in immune responses. This study was a logical extension of our previous work on lymphoid organs.

Marc K. Jenkins, Ph.D.
Distinguished McKnight University Professor
University of Minnesota Medical School
Department of Microbiology, Center for Immunology
Minneapolis, MN, USA