TY - JOUR
T1 - Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution
AU - Beura, Lalit K.
AU - Anderson, Kristin G.
AU - Schenkel, Jason M.
AU - Locquiao, Jeremiah J.
AU - Fraser, Kathryn A.
AU - Vezys, Vaiva
AU - Pepper, Marion
AU - Masopust, David
N1 - Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - Homing
UR - http://www.scopus.com/inward/record.url?scp=84929161091&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929161091&partnerID=8YFLogxK
U2 - 10.1189/jlb.1HI0314-154R
DO - 10.1189/jlb.1HI0314-154R
M3 - Article
C2 - 25395301
AN - SCOPUS:84929161091
SN - 0741-5400
VL - 97
SP - 217
EP - 225
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 2
ER -