Program in Molecular Medicine; Department of Pathology
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunology of Infectious Disease | Immunopathology | Molecular Biology | Virology
Profound type I interferon (IFN-I)-dependent attrition of memory CD8 and CD4 T cells occurs early during many infections. It is dramatic at 2 to 4 days following lymphocytic choriomeningitis virus (LCMV) infection of mice and can be elicited by the IFN-inducing Toll receptor agonist poly(I:C). We show that this attrition occurs in many organs, indicating that it is due to T cell loss rather than redistribution. This loss correlated with elevated intracellular staining of T cells ex vivo for activated caspases but with only low levels of ex vivo staining with annexin V, probably due to the rapid clearance of apoptotic cells in vivo. Instead, a high frequency of annexin V-reactive CD8alpha(+) dendritic cells (DCs), which are known to be highly phagocytic, accumulated in the spleen as the memory T cell populations disappeared. After short in vitro incubation, memory phenotype T cells isolated from LCMV-infected mice (day 3) or mice treated with poly(I:C) (12 h) displayed substantial DNA fragmentation, as detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, compared to T cells isolated from uninfected mice, indicating a role for apoptosis in the memory T cell attrition. This apoptosis of memory CD8 T cells early during LCMV infection was reduced in mice lacking the proapoptotic molecule Bim. Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells.
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Citation: J Virol. 2010 May;84(10):4866-77. doi: 10.1128/JVI.02571-09. Epub 2010 Mar 3. Link to article on publisher's site
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Bahl, Kapil; Hubner, Anette; Davis, Roger J.; and Welsh, Raymond M., "Analysis of apoptosis of memory T cells and dendritic cells during the early stages of viral infection or exposure to toll-like receptor agonists" (2010). Davis Lab. 85.