Co-infection alters CD8 T cell immunity and immunoprotection (105.27)

Abstract

Abstract Co-infection with multiple pathogens can result in increased pathology and difficulties with diagnosis and treatment. Moreover, interference between co-administered vaccines has resulted in lower antibody production. However, the effect of co-infections on T cell responses remains poorly understood. We have shown that sequential infection with unrelated viruses can alter T cell responses and disease outcome. This is defined as heterologous immunity, which is mediated by crossreactive T cells. We questioned if co-infection with two viruses containing a crossreactive epitope would alter the immune response and disease outcome upon rechallenge. Compared to mice infected with a single virus, rechallenged of mice co-infected with lymphocytic choriomenigitis (LCMV) and Pichinde viruses (PV) had a loss of immunoprotection and enhanced immunopathology. Each viral rechallenge identified a different potential mechanism to explain these changes. First, co-infection resulted in fewer LCMV-specific effector-like memory CD8 T cells leading to decreased protection and enhanced liver pathology. Secondly, co-infection caused some mice to have inappropriately enhanced crossreactive responses, which contributed to increased immunopathology. As combined vaccines or simultaneous immunizations are also co-infections, our data would suggest that T cell responses should be examined in the context of vaccine development.