Chronic Virus Infection Compromises non-virus-specific T cell Responses numerically and functionally

Chronic viral infections are widespread among humans, with approximately 8-12 chronic viral infections per individual and there is epidemiological evidence that these impair immune responses against other microbial challenges. We used an experimental chronic virus infection in mice (chronic infection with the Lymphocytic Choriomeningitis virus, LCMV) to determine its impact on T lymphocytes (a subgroup of white blood cells that are a central part of adaptive immunity) with non-LCMV specificity. These "bystander" T lymphocytes exhibited specificity for a fragment of the chicken ovalbumin protein and had previously encountered their antigen, rendering them "antigen-experienced", or in other words, memory cells. We specifically asked the question whether and how chronic LCMV infection would affect the phenotype and function of these memory bystander T cells. We found that chronic LCMV infection had a profound effect on total numbers, phenotype and function of memory bystander T cells. Numerically, bystander memory T cells were dramatically reduced in presence of chronic LCMV infection. Phenotypically, memory bystander T cells adopted an RNA and protein expression profile normally found in recently activated T cells (effector cells) and these alterations were mainly due to direct interleukin 6 (IL-6, an inflammatory cytokine) signaling on memory bystander T cells. Functionally, bystander T cells were compromised in their ability to produce inflammatory cytokines and to proliferate upon antigen encounter. These phenotypic and functional changes were reversed upon transfer of the memory bystander T cells into hosts without chronic LCMV infection, indicating major cell-extrinsic contributions responsible for the diminished function of bystander T cells. These findings open new perspectives for immunity and vaccination during chronic viral infections.

Link to the publication in the external page "Journal of Experimental Medicine".