Activation of antigen-specific CD8 T cells results in minimal killing of bystander bacteria.
Memory CD8 T cells play a critical role in protective immunity against intracellular pathogens. In addition to their ability to specifically recognize and lyse infected targets, activated CD8 T cells secrete cytokines that induce phagocytic cells to engulf and kill bacterial pathogens. In this study, we asked whether activation of Ag-specific CD8 T cells results in nonspecific killing of bystander bacteria during a mixed infection. Mice with epitope-specific memory CD8 T cells were coinfected with two isogenic strains of recombinant Listeria monocytogenes that differ in the cognate epitope. Recall responses by epitope-specific CD8 T cells rapidly inhibited the growth of epitope-bearing bacteria, impeding the course of infection within 6 h after challenge. This rapid inhibition was highly specific and did not affect the growth of coinfecting bacteria without the epitope. CTL recall did not enhance activation of innate immune cells, as evidenced by the absence of inducible NO synthase production in infectious foci. Our observations demonstrate the remarkable specificity of the bactericidal mechanisms of CTL and reveal the possibility for escape mutants to prevail in the hostile environment of a specific immune response. This implication has a bearing on subunit vaccine design strategies and understanding failure of immunization against bacterial infection.
Jiang
Jiu
J
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Zenewicz
Lauren A
LA
San Mateo
Lani R
LR
Lau
Lisa L
LL
Shen
Hao
H
D000595:Amino Acid Sequence; D000818:Animals; D024201:Bystander Effect / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D009698:Nucleoproteins; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus