Culling of activated CD4 T cells during typhoid is driven by Salmonella virulence genes.
Pathogen-specific CD4 T cells are activated within a few hours of oral Salmonella infection and are essential for protective immunity. However, CD4 T cells do not participate in bacterial clearance until several weeks after infection, suggesting that Salmonella can inhibit or evade CD4 T cells that are activated at early time points. Here, we describe the progressive culling of initially activated CD4 T cells in Salmonella-infected mice. Loss of activated CD4 T cells was independent of early instructional programming, T cell precursor frequency, and Ag availability. In contrast, apoptosis of Ag-specific CD4 T cells was actively induced by live bacteria in a process that required Salmonella pathogenicity island-2 and correlated with increased expression of PD-L1. These data demonstrate efficient culling of initially activated Ag-specific CD4 cells by a microbial pathogen and document a novel strategy for bacterial immune evasion.
Srinivasan
Aparna
A
Department of Medicine, Division of Gastroenterology, Center for Infectious Diseases and Microbiology Translational Research, McGuire Translational Research Facility, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Nanton
Minelva
M
Griffin
Amanda
A
McSorley
Stephen J
SJ
D000818:Animals; D017209:Apoptosis; D018122:B7-1 Antigen / Q000276:immunology; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002469:Cell Separation / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019081:O Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D012475:Salmonella / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D014435:Typhoid Fever / Q000276:immunology*; D014774:Virulence
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D019081:O Antigens; D010455:Peptides