Research Driven by Curiosity: The Journey from Basic Molecular Biology and Virology to Studies of Human Pathogenic Coronaviruses

Perlman, Stanley

CD8 T cells are important for MHV clearance, but they did not appear to be the main factor in immunopathological disease. The second major discovery was that another type of T cell, the CD4 T cell, was the major factor in host tissue damage in MHV-infected mice, and that virus-specific CD4 T cells were responsible for much of the tissue destruction and clinical disease. These results led to questions about how the immune response is normally turned off after virus clearance to prevent tissue damage and why this was not completely successful in MHV-infected animals. The third discovery, addressing these questions, was the identification of small numbers of virus-specific regulatory CD4 T cells, which turn off harmful immune responses, especially those caused by virus-specific CD4 T cells. This observation, in turn, raised questions about why these cells were present in only low numbers in the infected host and raised the possibility that these cells represent a therapeutic option in patients with viral encephalitis or other infectious diseases with an immunopathological component.