Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution

LK Beura, KG Anderson, JM Schenkel… - Journal of Leucocyte …, 2015 - academic.oup.com
LK Beura, KG Anderson, JM Schenkel, JJ Locquiao, KA Fraser, V Vezys, M Pepper
Journal of Leucocyte Biology, 2015academic.oup.com
Vaccines are desired that maintain abundant memory T cells at nonlymphoid sites of
microbial exposure, where they may be anatomically positioned for immediate pathogen
interception. Here, we test the impact of antigen persistence on mouse CD8 and CD4 T cell
distribution and differentiation by comparing responses to infections with different strains of
LCMV that cause either acute or chronic infections. We used in vivo labeling techniques that
discriminate between T cells present within tissues and abundant populations that fail to be …
Abstract
Vaccines are desired that maintain abundant memory T cells at nonlymphoid sites of microbial exposure, where they may be anatomically positioned for immediate pathogen interception. Here, we test the impact of antigen persistence on mouse CD8 and CD4 T cell distribution and differentiation by comparing responses to infections with different strains of LCMV that cause either acute or chronic infections. We used in vivo labeling techniques that discriminate between T cells present within tissues and abundant populations that fail to be removed from vascular compartments, despite perfusion. LCMV persistence caused up to ∼30-fold more virus-specific CD8 T cells to distribute to the lung compared with acute infection. Persistent infection also maintained mucosal-homing α4β7 integrin expression, higher granzyme B expression, alterations in the expression of the TRM markers CD69 and CD103, and greater accumulation of virus-specific CD8 T cells in the large intestine, liver, kidney, and female reproductive tract. Persistent infection also increased LCMV-specific CD4 T cell quantity in mucosal tissues and induced maintenance of CXCR4, an HIV coreceptor. This study clarifies the relationship between viral persistence and CD4 and CD8 T cell distribution and mucosal phenotype, indicating that chronic LCMV infection magnifies T cell migration to nonlymphoid tissues.
Oxford University Press