Immunological karma: T cells reactive to old flu infections make unrelated viral infections worse

Childhood infection with Epstein-Barr virus (EBV) is often asymptomatic, while the same infection in adolescents and adults causes infectious mononucleosis (IM). Liisa Selin and colleagues from the University of Massachusetts Medical School now show how, in a strange twist of immunological karma, T cells specific to a previously encountered virus (such as the flu) may come back to haunt you, by overzealously responding to a subsequent, unrelated viral infection like EBV, thereby increasing the severity of the immune response and causing IM. Their results appear online on November 23 in advance of print publication in the December issue of the Journal of Clinical Investigation.

The authors found that, in patients with IM, memory CD8+ T cells specific to an epitope of the influenza virus encountered in a previous infection, also recognized and reacted to an epitope of the Epstein-Barr virus. These two epitopes, with only 33% similarity, stimulate different T cell activities, which in sum skew the immune response to EBV infection. Excessive lymphocyte proliferation contributes to the marked deviation in disease course and is symptomatic of IM.

Overall, this demonstration of cross-reactivity involving 2 immunodominant epitopes from 2 of the most common human viruses highlights the potential importance of cross-reactive T cells in human disease states.