Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution.
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.
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Lalit K
LK
Beura
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Kristin G
KG
Anderson
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Jason M
JM
Schenkel
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Jeremiah J
JJ
Locquiao
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Kathryn A
KA
Fraser
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Vaiva
V
Vezys
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Marion
M
Pepper
Department of Microbiology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA masopust@umn.edu.
David
D
Masopust
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D053804:Granzymes / Q000276:immunology; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D039001:Integrin alpha Chains / Q000276:immunology; D039441:Integrin alpha4 / Q000276:immunology; D039641:Integrin beta Chains / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D037181:Lectins, C-Type / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D019718:Receptors, CXCR4 / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053804:Granzymes; D039001:Integrin alpha Chains; D039441:Integrin alpha4; D039641:Integrin beta Chains; D037181:Lectins, C-Type; D019718:Receptors, CXCR4; D000099192:CD69 Antigens; C514936:CXCR4 protein, mouse; C091367:alpha E integrins; C091368:integrin beta7; C509214:Gzmb protein, mouse
CD8 T cells; homing